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Hereditary spastic paraplegia v1.308 | RTN2 | Nour Elkhateeb reviewed gene: RTN2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38527963; Phenotypes: Weakness in the distal upper and lower limbs, Lower limb spasticity, Hyperreflexia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.308 | SPG7 | Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.305 | SPG7 | Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, autosomal recessive to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.304 | SPAST | Sarah Leigh Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.300 | MAG | Arina Puzriakova Added comment: Comment on list classification: Promoted from Amber to Green and removed watchlist tag as there are now at least 12 individuals from 8 families with biallelic variants in this gene. Clinical features are characterised by spasticity (9/13), neuropathy (8/13), optic atrophy (7/13), variable cognitive deficits (7/13), and cerebellar signs (10/13) including ataxia in some (8/13) although 3/10 showed normal brain MRI results. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.299 | MAG | Arina Puzriakova Phenotypes for gene: MAG were changed from Spastic paraplegia 75, autosomal recessive, 616680 to Spastic paraplegia 75, autosomal recessive, OMIM:616680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.298 | SPAST | Achchuthan Shanmugasundram Publications for gene: SPAST were set to Hazan et al (1999) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.297 | KDM5C | Arina Puzriakova Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, OMIM:300534 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.294 | HSPD1 | Arina Puzriakova Added comment: Comment on mode of inheritance: Updated from 'monoallelic' only to 'both mono- and biallelic'. Biallelic variants cause a paediatric-onset leukodystrophy, with spasticity as a feature (MIM# 612233), while monoallelic variants have been associated with adult-onset HSP (MIM# 605280) - both phenotypes are relevant to this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.293 | HSPD1 | Arina Puzriakova Phenotypes for gene: HSPD1 were changed from Spastic paraplegia 13, autosomal dominant to Leukodystrophy, hypomyelinating, 4, OMIM:612233 (AR); Spastic paraplegia 13, autosomal dominant, OMIM:605280 (AD) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.291 | C19orf12 | Sarah Leigh Phenotypes for gene: C19orf12 were changed from to ?Spastic paraplegia 43, autosomal recessive, OMIM:615043; Neurodegeneration with brain iron accumulation 4, OMIM: 614298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.276 | RNASEH2B | Arina Puzriakova Phenotypes for gene: RNASEH2B were changed from Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis to Aicardi-Goutieres syndrome 2, OMIM:610181 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.275 | RAB3GAP2 | Arina Puzriakova Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia; Warburg micro syndrome 2, 614225 to Martsolf syndrome 1, OMIM:212720; Warburg micro syndrome 2, OMIM:614225 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.274 | IBA57 | Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Spastic paraplegia 74, autosomal recessive, 616451 to ?Spastic paraplegia 74, autosomal recessive, OMIM:616451 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.273 | AP5Z1 | Arina Puzriakova Phenotypes for gene: AP5Z1 were changed from Spastic Paraplegia, Recessive ; Spastic paraplegia 48, autosomal recessive to Spastic paraplegia 48, autosomal recessive, OMIM:613647 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.272 | KIDINS220 | Sarah Leigh Added comment: Comment on mode of pathogenicity: Personal communication from Dmitrijs Rots (RadboudUMC). Prompted by the occurrence of a KIDINS220 nonsense variant in the middle of the gene, in a family without spastic paraplegia (HSP) or other features; an in-depth analysis of KIDINS220 variants was performed. It would appear that KIDINS220 gene is tolerant of LOF variants (nonsense, frameshift) in gnomAD population (hence pLI~ 0, in the PanelApp review by Dmitrijs Rots (RadboudUMC), 4 Nov 2021). This was unexpected, as KIDINS220-associated-HSP presents in childhood, so it would appear that haploinsufficiency is unlikely as the mechanism. In addition, there were nonsense/frameshift HSP-associated variants in KIDINS220, but they were located in the last two exons of the gene and so likely to escape nonsense mediated decay. Therefore, it is proposed that rather a LOF mechanism a dominant negative effect may be responsible, however, further cases need to be identified to confirm this. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.267 | KIDINS220 | Sarah Leigh Phenotypes for gene: KIDINS220 were changed from Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296 to Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.259 | KIDINS220 | Dmitrijs Rots reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 33763417; Phenotypes: Spastic paraplegia, intellectual disability; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.258 | ABHD16A |
Ivone Leong gene: ABHD16A was added gene: ABHD16A was added to Hereditary spastic paraplegia. Sources: Expert Review Amber,Literature Q4_21_rating tags were added to gene: ABHD16A. Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABHD16A were set to 34587489 Phenotypes for gene: ABHD16A were set to Spastic paraplegia; Intellectual disability |
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Hereditary spastic paraplegia v1.256 | L1CAM | Arina Puzriakova Phenotypes for gene: L1CAM were changed from X-linked hydrocephalus, MASA syndrome, Hereditary spastic paraplegia to CRASH syndrome, OMIM:303350; MASA syndrome, OMIM:303350; Hydrocephalus due to aqueductal stenosis, OMIM:307000; Hydrocephalus with congential idiopathic intestinal pseudoobstruction, OMIM:307000; Hydrocephalus with Hirschsprung disease, OMIM:307000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.255 | C12orf65 | Arina Puzriakova Phenotypes for gene: C12orf65 were changed from Spasticparaplegia55,autosomalrecessive,615035 to Spastic paraplegia 55, autosomal recessive, OMIM:615035 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.254 | WDR45B | Arina Puzriakova Phenotypes for gene: WDR45B were changed from profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. to Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.253 | TFG | Arina Puzriakova Phenotypes for gene: TFG were changed from Hereditary spastic paraplegia - childhood onset; Intellectual disability; Hereditary spastic paraplegia - adult onset; neuropathy to Spastic paraplegia 57, autosomal recessive, OMIM:615658 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.250 | SPART | Arina Puzriakova Phenotypes for gene: SPART were changed from to Troyer syndrome, OMIM:275900; Spastic paraplegia 20 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.248 | REEP2 | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Amber to Green as there are now sufficient unrelated cases (>3) of spasticity associated with variants in this gene (updated references in publications list). REEP2 is also already Green on the GMS-equivalent HSP panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.247 | KIF1C | Arina Puzriakova changed review comment from: Comment on list classification: Upgraded from Amber to Green as there are now sufficient unrelated cases (>3) of spasticity associated with variants in this gene (updated references in publications list). KDM5C is also already Green on the GMS-equivalent HSP panels.; to: Comment on list classification: Upgraded from Amber to Green as there are now sufficient unrelated cases (>3) of spasticity associated with variants in this gene (updated references in publications list). KIF1C is also already Green on the GMS-equivalent HSP panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.246 | NKX6-2 | Arina Puzriakova Phenotypes for gene: NKX6-2 were changed from Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 to Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, OMIM:617560 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.245 | KIF1C | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Amber to Green as there are now sufficient unrelated cases (>3) of spasticity associated with variants in this gene (updated references in publications list). KDM5C is also already Green on the GMS-equivalent HSP panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.243 | KIF1C | Arina Puzriakova Phenotypes for gene: KIF1C were changed from Spastic ataxia 2,autosomal recessive to Spastic ataxia 2, autosomal recessive, OMIM:611302 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.240 | KDM5C | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Amber to Green as there are now sufficient unrelated cases (>3) of spastic paraplegia with variants in this gene (updated references in publications list). KDM5C is also already Green on the GMS-equivalent HSP panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.238 | ENTPD1 | Arina Puzriakova Phenotypes for gene: ENTPD1 were changed from Spasticparaplegia64,615683 to Spastic paraplegia 64, autosomal recessive, OMIM:615683 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.235 | ENTPD1 | Arina Puzriakova reviewed gene: ENTPD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30652007; Phenotypes: Spastic paraplegia 64, autosomal recessive, OMIM:615683; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.235 | ARG1 | Arina Puzriakova Phenotypes for gene: ARG1 were changed from Argininaemia, 207800; Progressive spastic tetraplegia to Argininemia, OMIM:207800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.234 | ALS2 | Arina Puzriakova Phenotypes for gene: ALS2 were changed from 607225 to Amyotrophic lateral sclerosis 2, juvenile, OMIM:205100; Primary lateral sclerosis, juvenile, OMIM:606353; Spastic paralysis, infantile onset ascending, OMIM:607225 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.231 | KIF1A | Arina Puzriakova Phenotypes for gene: KIF1A were changed from Spastic paraplegia 30, autosomal recessive to Spastic paraplegia 30, autosomal dominant, OMIM:610357; Spastic paraplegia 30, autosomal recessive, OMIM:610357; NESCAV syndrome, OMIM:614255 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.228 | WASHC5 | Ivone Leong Phenotypes for gene: WASHC5 were changed from Spastic paraplegia 8, autosomal dominant to Spastic paraplegia 8, autosomal dominant, OMIM:603563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.227 | BSCL2 | Arina Puzriakova Phenotypes for gene: BSCL2 were changed from Silver spastic paraplegia syndrome, to Silver spastic paraplegia syndrome, OMIM:270685 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.225 | CYP7B1 | Arina Puzriakova Phenotypes for gene: CYP7B1 were changed from Spastic paraplegia 5A, autosomal recessive to Spastic paraplegia 5A, autosomal recessive , OMIM:270800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.223 | HIKESHI |
Ivone Leong gene: HIKESHI was added gene: HIKESHI was added to Hereditary spastic paraplegia. Sources: Expert Review Amber,Expert list Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HIKESHI were set to 26545878; 28000699 Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, OMIM:616881 |
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Hereditary spastic paraplegia v1.222 | POLR3K |
Ivone Leong gene: POLR3K was added gene: POLR3K was added to Hereditary spastic paraplegia. Sources: Expert Review Amber,Literature watchlist, founder-effect tags were added to gene: POLR3K. Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3K were set to 30584594; 33659930 Phenotypes for gene: POLR3K were set to Leukodystrophy, hypomyelinating, 21, OMIM:619310 |
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Hereditary spastic paraplegia v1.221 | AFG3L2 | Sarah Leigh Phenotypes for gene: AFG3L2 were changed from Ataxia, spastic, 5, autosomal recessive; Spastic ataxia 5, autosomal recessive to Spastic ataxia 5, autosomal recessive OMIM:614487; spastic ataxia 5 MONDO:0013776; Spinocerebellar ataxia 28 OMIM:610246; spinocerebellar ataxia type 28 MONDO:0012450 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.219 | AP4E1 | Arina Puzriakova Phenotypes for gene: AP4E1 were changed from Spastic paraplegia 51, autosomal recessive to Spastic paraplegia 51, autosomal recessive, OMIM:613744; Hereditary spastic paraplegia 51, MONDO:0013401 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.218 | AP4B1 | Arina Puzriakova Phenotypes for gene: AP4B1 were changed from Spastic paraplegia 47, autosomal recessive to Spastic paraplegia 47, autosomal recessive, OMIM:614066; Hereditary spastic paraplegia 47, MONDO:0013551 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.216 | SARS2 |
Sarah Leigh gene: SARS2 was added gene: SARS2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SARS2 were set to 21255763; 24034276; 27279129 Phenotypes for gene: SARS2 were set to Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845; Progressive Spastic Paresis Review for gene: SARS2 was set to AMBER Added comment: PMID 27279129 reports a child with progressive spastic paresis with a homozygous splicing variant (c.1347G>A (NM_017827.3)), which was shown in vitro to result in retention of intron 14 and premature chain termination, leading to diminished levels of the synthetase in patient's fibroblasts. Sources: Literature |
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Hereditary spastic paraplegia v1.215 | PCYT2 | Eleanor Williams Phenotypes for gene: PCYT2 were changed from Complex hereditary spastic paraplegia; Spastic paraplegia 82, autosomal recessive #618770 to Complex hereditary spastic paraplegia; Spastic paraplegia 82, autosomal recessive, 618770 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.214 | PCYT2 | Eleanor Williams Phenotypes for gene: PCYT2 were changed from Complex hereditary spastic paraplegia to Complex hereditary spastic paraplegia; Spastic paraplegia 82, autosomal recessive #618770 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.212 | TFG | Louise Daugherty Phenotypes for gene: TFG were changed from to Hereditary spastic paraplegia - childhood onset; Intellectual disability; Hereditary spastic paraplegia - adult onset; neuropathy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.210 | TFG | Zerin Hyder reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: None; Publications: 23479643, 27601211, 28124177, 27492651; Phenotypes: Hereditary spastic paraplegia - childhood onset, Intellectual disability, Hereditary spastic paraplegia - adult onset; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.210 | RNASEH2B | Louise Daugherty Added comment: Comment on list classification: New gene added. The 100,000 Genomes Project has identified one case and recent publications have reported RNASEH2B variants in homozygous status in patients with spastic paraplegia. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.209 | RNASEH2B | Louise Daugherty Phenotypes for gene: RNASEH2B were changed from spastic paraparesis to Aicardi-Goutieres syndrome 2, 610181; spastic paraparesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.207 | RNASEH2B |
Zerin Hyder gene: RNASEH2B was added gene: RNASEH2B was added to Hereditary spastic paraplegia. Sources: Other Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473 Phenotypes for gene: RNASEH2B were set to spastic paraparesis Penetrance for gene: RNASEH2B were set to unknown Mode of pathogenicity for gene: RNASEH2B was set to Other Review for gene: RNASEH2B was set to GREEN Added comment: Abovepublications report association of pure, childhood-onset spastic paraparesis in association with missense recessive variants in RNASEH2B. Sources: Other |
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Hereditary spastic paraplegia v1.206 | PCYT2 |
Louise Daugherty gene: PCYT2 was added gene: PCYT2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to Complex hereditary spastic paraplegia Review for gene: PCYT2 was set to GREEN Added comment: New publication (2019) : Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia: Vaz, Frédéric M et.al., PMID: 31637422. Identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy. CTP:phosphoethanolamine cytidylyltransferase (ET) is encoded by the PCYT2 gene. Using patient fibroblasts they demonstrated that the variants were hypomorphic, resulting in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR- Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. The data establishes that PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirmed that etherlipid homeostasis is important for the development and function of the brain. Sources: Literature |
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Hereditary spastic paraplegia v1.203 | REEP2 | Louise Daugherty commented on gene: REEP2: Gene to be reviewed again after the GMS Neurology specialist test group have reviewed and agreed rating of gene on the Hereditary spastic paraplegia - childhood onset panel on May 2019 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.203 | REEP2 | Louise Daugherty edited their review of gene: REEP2: Added comment: Gene to be reviewed again after the GMS Neurology specialist test group have reviewed and agreed rating of gene on the Hereditary spastic paraplegia - childhood onset panel on May 2019; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.197 | UBAP1 |
Louise Daugherty gene: UBAP1 was added gene: UBAP1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: UBAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: UBAP1 were set to 30929741 Phenotypes for gene: UBAP1 were set to Hereditary spastic paraplegia Review for gene: UBAP1 was set to GREEN Added comment: PMID:30929741 reported the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1. Sources: Literature |
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Hereditary spastic paraplegia v1.196 | EIF2B5 |
Chris Buxton gene: EIF2B5 was added gene: EIF2B5 was added to Hereditary spastic paraplegia. Sources: Expert list Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EIF2B5 were set to See OMIM https://www.omim.org/entry/603896 Phenotypes for gene: EIF2B5 were set to progressive cerebellar ataxia; spasticity; cognitive impairment Penetrance for gene: EIF2B5 were set to unknown Mode of pathogenicity for gene: EIF2B5 was set to Other Review for gene: EIF2B5 was set to AMBER gene: EIF2B5 was marked as current diagnostic Added comment: Curerntly diagnostic on Sheffield's HSP panel. Vanishing white matter leukodystrophy: Phenotype could be theoretically interpreted as HSP in an infant? so maybe only consider for Child onset HSP panel. HGMD mostly lists missense variants Sources: Expert list |
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Hereditary spastic paraplegia v1.196 | NT5C2 | Rebecca Foulger Phenotypes for gene: NT5C2 were changed from Spasticparaplegia 45, autosomal recessive, 613162 to Spastic paraplegia 45, autosomal recessive, 613162 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.195 | NT5C2 | Rebecca Foulger Phenotypes for gene: NT5C2 were changed from Spasticparaplegia 45, autosomal recessive 613162 to Spasticparaplegia 45, autosomal recessive, 613162 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.194 | NT5C2 | Rebecca Foulger Phenotypes for gene: NT5C2 were changed from Spasticparaplegia45, autosomal recessive 613162 to Spasticparaplegia 45, autosomal recessive 613162 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.193 | NT5C2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green based on curation by Sarah Leigh and feedback from Helen Brittain who notes that there are sufficient cases with a phenotype that includes spasticity to meet the threshold for inclusion; therefore a green rating seems appropriate. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.191 | IBA57 | Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber following clinical review by Helen Brittain, who notes that it is possible that the varied phenotypes are part of the spectrum of presentations within IBA57 regarding its mitochondrial function (the more commonly reported recessive phenotype of mitochondrial dysfunction encompasses spasticity in several patients). IBA57 is green on the 'Mitochondrial disorders' panel which is the better route for detecting this broader phenotype. Ideally, further cases with an understanding of the spectrum of pathogenic variants and detailed phenotypic information will help in being confident about inclusion on this HSP panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.186 | SLC2A1 | Rebecca Foulger Phenotypes for gene: SLC2A1 were changed from Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia to Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia; autosomal dominant, complicated hereditary spastic paraplegia (HSP) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.184 | HACE1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after clinical advice from Helen Brittain who says that Progressive spasticity seems to be a clear feature and there are sufficient cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.181 | GBA2 | Louise Daugherty Phenotypes for gene: GBA2 were changed from Spastic paraplegia 46, autosomal recessive to Spastic paraplegia 46, autosomal recessive, 614409 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.178 | SLC2A1 | Rebecca Foulger commented on gene: SLC2A1: PMID:21832227 (Weber et al 2011) identified causative variants in SLC2A1 in a German/Dutch family and an Australian monozygotic twin pair with Dystonia. In their cohort of HSP patients, one missense variant (c.138G>C/p.Q46H) was detected in one case of German origin but functional studies indicated the variant was likely benign. The authors conclude that slowly progressive spastic paraparesis complicated by PED can therefore be regarded as a novel phenotype associated with SLC2A1 mutations. However, GLUT1 defects do not seem to play a major role in other forms of autosomal dominant HSP, as suggested by the absence of pathogenic mutations in 139 HSP index patients. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.178 | RAB3GAP2 | Rebecca Foulger Phenotypes for gene: RAB3GAP2 were changed from spastic paraplegia to spastic paraplegia; Warburg micro syndrome 2, 614225 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.176 | RAB3GAP2 | Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Red by Chris Buxton (Bristol NHS). Kept rating as Red based on expert review and limited cases, as reviewed by Chris Buxton. OMIM lists progressive spastic diplegia to quadriplegia as a clinical symptom of Warburg micro syndrome 2, 614225. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.173 | LYST | Rebecca Foulger Phenotypes for gene: LYST were changed from spastic paraplegia to spastic paraplegia; Chediak-Higashi syndrome, 214500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.170 | LYST | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Gene added to panel by Chris Buxton (Bristol NHS) based on one family in PMID:24521565. In addition, progressive spastic paraparesis seen in affected siblings in PMID:26307451, and PMIDs 25519960 and 25519961 describe LYST as a potential HSP locus. Further cases required for a diagnostic rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.169 | LYST | Rebecca Foulger commented on gene: LYST: PMID:6307451 (Desai et al 2016) report 3 affected siblings with the late-onset form of CHS, and phenotypes including progressive spastic paraparesis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.168 | KLC4 | Rebecca Foulger Phenotypes for gene: KLC4 were changed from spastic paraplegia to spastic paraplegia; progressive complicated spastic paraplegia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.167 | KDM5C | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber. Gene added to panel and rated Red by Chris Buxton (Bristol NHS). MIM:300534 is characterized by ID, progressive spastic paraplegia, short stature, microcephaly, and dysmorphic facial appearance. Chris Buxton reports 2 families from the literature (PMIDs10982473; 15586325; 26919706) with KDM5C variants and spastic paraplegia symptoms. Therefore Amber awaiting further cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.166 | KDM5C |
Rebecca Foulger commented on gene: KDM5C: PMID:26919706 investigated a family of 3 boys with ID and among them identified two different variants in KDM5C: Two affected boys have c.633delG and the other has c.631delC. The boys presented with severe DD, progressive spasticity (predominantly in the lower limbs), epilepsy and subclinical hypothyroidism. The mother has two different frameshift mutations: a heterozygous germline mutation, c.631delC, and a low-prevalence somatic mutation, c.633delG. |
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Hereditary spastic paraplegia v1.166 | KDM5C | Rebecca Foulger Phenotypes for gene: KDM5C were changed from Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism to Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534; Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.165 | HACE1 | Rebecca Foulger Phenotypes for gene: HACE1 were changed from Spastic paraplegia; psychomotor retardation; seizure to Spastic paraplegia; psychomotor retardation; seizure; Spastic paraplegia and psychomotor retardation with or without seizures, 616756 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.164 | HACE1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber awaiting further clinical review. Gene added to panel and rated Amber by Chris Buxton (Bristol NHS) based on >3 cases of patients with 'Spastic paraplegia and psychomotor retardation with or without seizures, 616756' from 2 papers (Hollstein et al., 2015/PMID:26424145 and Akawi et al., 2015/PMID:26437029). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.163 | ERLIN1 | Rebecca Foulger Phenotypes for gene: ERLIN1 were changed from Hereditary spastic paraplegia to Hereditary spastic paraplegia; Spastic paraplegia 62, 615681 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.161 | DARS | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber to match expert review and literature evidence. Added to panel and rated Amber by Chris Buxton (Bristol NHS). 2 patients in PMID:25527264 with onset in late adolescence who presented with subacute spastic paraplegia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.160 | DARS | Rebecca Foulger Phenotypes for gene: DARS were changed from Brain stem and spinal cord Hypomyelination; leg spasticity to Brain stem and spinal cord Hypomyelination; leg spasticity; Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.158 | CYP27A1 | Rebecca Foulger Phenotypes for gene: CYP27A1 were changed from progressive lower extremity spasticity,often disproportionate to any degree of weakness to Cerebrotendinous xanthomatosis, 213700; progressive lower extremity spasticity,often disproportionate to any degree of weakness | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.157 | CYP27A1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber awaiting further clinical review. CYP27A1 was added to panel and rated Amber by Chris Buxton (Bristol NHS). Multiple cases from literature of spastic paresis presenting with Cerebrotendinous xanthomatosis (CTX), which is caused by variants in CYP27A1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.155 | CYP27A1 | Rebecca Foulger commented on gene: CYP27A1: PMID:29321515 (Sekijima et al, 2018) conducted a Japanese survey on Cerebrotendinous xanthomatosis (CTX). The most common initial symptom was tendon xanthoma, followed next by spastic paraplegia, cognitive dysfunction, cataract, ataxia, and epilepsy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.155 | CYP27A1 | Rebecca Foulger commented on gene: CYP27A1: PMID:27455001 (Zhang et al 2017) report a 27 year old male with mental retardation and subsequently memory lapses, ataxia, spastic paraplegia and fuzzy language. The patient was found to have a compound het variant in CYP27A1. The article is in Chinese, preventing further reading. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.155 | CYP27A1 | Rebecca Foulger commented on gene: CYP27A1: PMID:28623566 (Chen et al 2017) investigated clinical symptoms of Chinese CTX patients. Three novel variants of p.Arg513Cys, c.1477-2A>C in family 1 and p.Arg188Stop in family 4 (NM 000784.3) in CYP27A1 were found. The probands in the study manifested cerebellar ataxia, tendon xanthoma and spastic paresis in family 1 and 4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.155 | CYP27A1 | Rebecca Foulger commented on gene: CYP27A1: PMID:26874936 (Rasafio et al 2016) report 2 Italian siblings from a consanguineous family with Cerebrotendinous xanthomatosis and different phenotypes but the same G-to-A transition causing splicing alteration. The 41 year old male presented with mutacism, spastic tetraparesis, bilateral pes cavus, sialorrhea, progressive dysphagia and head dystonia. Genetic testing of other family members revealed the same variant in a sister who had mild spastic paraparesis amongst her symptoms, and a status of asymptomatic carriers of heterozygous mutation in two sisters. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.155 | ATP13A2 | Rebecca Foulger Phenotypes for gene: ATP13A2 were changed from Adult-onset lower-limb predominant spastic paraparesis to Adult-onset lower-limb predominant spastic paraparesis; Spastic paraplegia 78, autosomal recessive, 617225; complicated hereditary spastic paraplegia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.152 | ATP13A2 | Rebecca Foulger Added comment: Comment on list classification: Updating rating from Red to Green based on literature evidence. ATP13A2 was added to panel and rated Red by Chris Buxton (Bristol NHS) although he provides evidence of 3 unrelated cases in PMID:28137957. PMID:27217339 (Kara et al 2016) provides evidence of an additional case. Therefore sufficient (4) unrelated cases to support diagnostic rating, and ATP13A2 is associated with Spastic paraplegia 78, autosomal recessive, 617225 in OMIM. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.151 | ATP13A2 | Rebecca Foulger commented on gene: ATP13A2: In a 46-year-old man (proband 41), born of consanguineous Pakistani parents, with AR spastic paraplegia, Kara et al. (2016, PMID:27217339) identified a homozygous 3-bp deletion (c.3020_3022del, NM_001141974.2), resulting in an in-frame deletion (Phe1007del). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.151 | ARG1 | Rebecca Foulger Phenotypes for gene: ARG1 were changed from Argininaemia; Progressive spastic tetraplegia to Argininaemia, 207800; Progressive spastic tetraplegia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.149 | ARG1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: ARG1 was added to the panel by Chris Buxton (Bristol NHS). Sufficient cases from PMID:23859858 (which overlaps with PMID:26310552) to support causation of progressive spastic tetraplegia. Additional cases are reported on OMIM: spastic tetraplegia was seen in a Japanese girl with argininemia and compound het variants in ARG1 (PMID:2365823, Haraguchi et al 1990), and in a Japanese patient identified by Uchino et al, 1992 (PMID:1463019) with compound het variants in ARG1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.148 | ARG1 | Rebecca Foulger commented on gene: ARG1: Wu (2013, 23859858) is very similar to PMID:26310552. They investigated 5 Chinese patients (3 boys, 2 girls) with argininemia in whom it mainly manifested as progressive spastic tetraplegia. Homozygous variants in ARG1 were found in patients 1 and 5, and compound het variants were found in patients 2, 3 and 4. Although not explicitly stated, from the text it sounds like the patients are not related. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.148 | ABCD1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green. ABCD1 was added to panel and rated Green by Chris Buxton (Bristol NHS). Sufficient unrelated cases (>3) of patients with HSP phenotype and ABCD1 variant to support causation of spastic paraplegia (see comments on individual papers for details). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.147 | ABCD1 | Rebecca Foulger Phenotypes for gene: ABCD1 were changed from Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis; Adrenoleukodystrophy, 300100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.146 | ABCD1 | Rebecca Foulger Phenotypes for gene: ABCD1 were changed from Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation; spastic paraparesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.144 | ABCD1 | Rebecca Foulger commented on gene: ABCD1: Koutsis (2015, 26049658) report a Greek family with 5 males and 2 females developing progressive spastic paraplegia. NGS of the proband revealed a novel frameshift mutation in ABCD1 (c.1174_1178del, p.Leu392Serfs*7), which segregated in all family members. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.144 | ABCD1 | Rebecca Foulger commented on gene: ABCD1: Balicza (2016, 27084228) carried out genetic testing for 58 probands with clinical features of HSP. Results included one hemizygous variant in ABCD1 (c.1553G>C, p.Arg518Pro) in a male patient with sporadic spastic paraparesis. His disease started at age 28. The authors report that there are other similar cases where ABCD1 variants mimic HSP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.127 | IBA57 | Rebecca Foulger Phenotypes for gene: IBA57 were changed from spastic paraplegia to ?Spastic paraplegia 74, autosomal recessive, 616451 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.125 | IBA57 | Rebecca Foulger commented on gene: IBA57: PMID:30258207 (Hamanaka et al, 2018) performed whole-exome sequencing in 2 unrelated families (Sepharadi Jewish and Japanese) with leukodystrophy. The 29-year-old Sepharadi Jewish male had clinically asymptomatic leukodystrophy. His 19-year-old younger brother, with the same compound heterozygous IBA57 variants, had a similar clinical course until 7 years of age when he developed a rapidly progressive spastic paraparesis following a febrile illness. A 7-year-old Japanese girl had developmental regression, spastic quadriplegia, and abnormal periventricular white matter. Therefore HSP symptoms amongst the individuals but phenotypes are very varied. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.123 | GCH1 | Rebecca Foulger Phenotypes for gene: GCH1 were changed from Dystonia; Spastic paraplegia; progressive spastic paraplegia; dopa-responsive dystonia (DRD) to Dystonia; Spastic paraplegia; progressive spastic paraplegia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.122 | GCH1 | Rebecca Foulger Phenotypes for gene: GCH1 were changed from Dystonia; Spastic paraplegia to Dystonia; Spastic paraplegia; progressive spastic paraplegia; dopa-responsive dystonia (DRD) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.120 | FARS2 | Rebecca Foulger commented on gene: FARS2: In 2 unrelated patients with mitochondrial dysfunction and spastic paraplegia, Vantroys et al. (2017, PMID:29126765) identified compound heterozygous variants in the FARS2 gene: (c.1082C-T, NM_006567.4, P361L) in both probands, combined with A154V in proband 1, and a 3-bp deletion (c.521_523delTGG) in proband 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.120 | FARS2 | Rebecca Foulger commented on gene: FARS2: In 2 sibs with mitochondrial dysfunction and spastic paraplegia, Vernon et al. (2015, PMID:25851414) identified compound het variants in the FARS2 gene: a paternally inherited R419C and a maternally inherited 116-kb interstitial deletion including all of exon 6 and parts of introns 5 and 6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.120 | FARS2 | Rebecca Foulger commented on gene: FARS2: In 4 sibs, born of consanguineous Chinese parents, with AR spastic paraplegia, Yang et al. (2016, PMID:26553276) identified a homozygous transversion (c.424G-T, NM_006567.3) in the FARS2 gene (D142Y). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.119 | FARS2 | Rebecca Foulger Phenotypes for gene: FARS2 were changed from spastic paraplegia to Spastic paraplegia 77, autosomal recessive, 617046 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.116 | MAG | Rebecca Foulger commented on gene: MAG: In 3 siblings with AR spastic paraplegia born of consanguineous Palestinian parents, Lossos et al. (2015, PMID:26179919) identified a homozygous c.399C-G transversion in the MAG gene (S133R). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.116 | MAG | Rebecca Foulger Phenotypes for gene: MAG were changed from spastic paprplegia to Spastic paraplegia 75, autosomal recessive, 616680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.111 | NT5C2 | Sarah Leigh Phenotypes for gene: NT5C2 were changed from Spasticparaplegia45,613162 to Spasticparaplegia45, autosomal recessive 613162 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.94 | TBP_CAG |
Arianna Tucci STR: TBP_CAG was added STR: TBP_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: TBP_CAG was marked as current diagnostic |
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Hereditary spastic paraplegia v1.92 | PPP2R2B_CAG |
Arianna Tucci STR: PPP2R2B_CAG was added STR: PPP2R2B_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: PPP2R2B_CAG was marked as current diagnostic |
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Hereditary spastic paraplegia v1.90 | ATXN10_ATTCT |
Arianna Tucci STR: ATXN10_ATTCT was added STR: ATXN10_ATTCT was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: ATXN10_ATTCT was marked as current diagnostic |
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Hereditary spastic paraplegia v1.88 | ATXN7_CAG |
Arianna Tucci STR: ATXN7_CAG was added STR: ATXN7_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: ATXN7_CAG was marked as current diagnostic |
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Hereditary spastic paraplegia v1.86 | CACNA1A_CAG |
Arianna Tucci STR: CACNA1A_CAG was added STR: CACNA1A_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: CACNA1A_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: CACNA1A_CAG was marked as current diagnostic |
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Hereditary spastic paraplegia v1.84 | ATXN3_CAG |
Arianna Tucci STR: ATXN3_CAG was added STR: ATXN3_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted STR: ATXN3_CAG was marked as current diagnostic |
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Hereditary spastic paraplegia v1.82 | ATXN2_CAG |
Arianna Tucci STR: ATXN2_CAG was added STR: ATXN2_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results Sources: Expert Review |
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Hereditary spastic paraplegia v1.80 | ATXN1_CAG |
Arianna Tucci STR: ATXN1_CAG was added STR: ATXN1_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Review for STR: ATXN1_CAG was set to GREEN Added comment: Sources: Expert Review |
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Hereditary spastic paraplegia v1.75 | HTT_CAG |
Arianna Tucci STR: HTT_CAG was added STR: HTT_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Review for STR: HTT_CAG was set to GREEN Added comment: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back HTT results Sources: Expert Review |
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Hereditary spastic paraplegia v1.73 | FXN_GAA |
Arianna Tucci STR: FXN_GAA was added STR: FXN_GAA was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal STR: FXN_GAA was marked as current diagnostic Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results Sources: Expert Review |
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Hereditary spastic paraplegia v1.71 | HACE1 |
Chris Buxton gene: HACE1 was added gene: HACE1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HACE1 were set to 26424145; 26437029 Phenotypes for gene: HACE1 were set to Spastic paraplegia; psychomotor retardation; seizure Penetrance for gene: HACE1 were set to unknown Review for gene: HACE1 was set to AMBER Added comment: Associated with 'Spastic paraplegia and psychomotor retardation with or without seizures' is an autosomal recessive complex neurodevelopmental disorder with onset in infancy Hollstein (2015, 26424145): Exome study, 2 families with 8 affected individuals with biallelic LoF variants. Absence of expressed protein shown by Western blots. Akawi (2015, 26437029) 6 patients from 4 unrelated families with SPPRS (truncal hypotonia and mixed spastic and dystonic tetraparesis) Sources: Literature |
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Hereditary spastic paraplegia v1.71 | DARS |
Chris Buxton gene: DARS was added gene: DARS was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DARS were set to 23643384; 25527264 Phenotypes for gene: DARS were set to Brain stem and spinal cord Hypomyelination; leg spasticity Penetrance for gene: DARS were set to unknown Review for gene: DARS was set to AMBER Added comment: HGMD: 15 missense, 1 ins associated with: Hypomyelination with brain stem and spinal cord involvement and leg spasticity: An autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation Taft (2013, 23643384) identiofied compound-heterozygous and homozygous DARS missense variants in 7 unrelated families with severe lower limb spasticity associated with leukoencephalopathy Phenotype expanded by Wolf (2015, 25527264) to later onset and subacute spastic paraplegia. Sources: Literature |
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Hereditary spastic paraplegia v1.71 | ATP13A2 |
Chris Buxton gene: ATP13A2 was added gene: ATP13A2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP13A2 were set to 28137957 Phenotypes for gene: ATP13A2 were set to Adult-onset lower-limb predominant spastic paraparesis Penetrance for gene: ATP13A2 were set to unknown Review for gene: ATP13A2 was set to RED Added comment: Estrada-Cuzcano (2017, 28137957). Biallelic LoF varaints cause complicated hereditary spastic paraplegia. Exome study identified biallelic missense . Further analysis of 795 HSP /erlated disorders identified 2 families with truncating ATP13A2 variants. Some supportive functional studies. Clin: Adult-onset lower-limb predominant spastic paraparesis Sources: Literature |
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Hereditary spastic paraplegia v1.71 | SLC2A1 |
Chris Buxton gene: SLC2A1 was added gene: SLC2A1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: SLC2A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC2A1 were set to 11136715; 21832227; 18606970 Phenotypes for gene: SLC2A1 were set to Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia Penetrance for gene: SLC2A1 were set to unknown Review for gene: SLC2A1 was set to RED Added comment: Spastic diplegia described as a component phenotype with a more complex presentation Klepper (2001, 11136715) described diplegic spasticity associated with other dev delay and seizure phenotype in sibs with a het GLUT1 variant. Weber (2011, 21832227) desribed childhood onset paroxysmal choreoathetosis and progressive spastic paraplegia and het varaints in SLC2A1. Zorzi (2008, 18606970) described a 22yo Italian woman with het denovo missense in SLC2A1 with delayed psychomotor development, mild mental retardation, microcephaly, dysarthria, and spasticity. Diagnostic on Sheffield HSP panel. Sources: Literature |
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Hereditary spastic paraplegia v1.71 | RAB3GAP2 |
Chris Buxton gene: RAB3GAP2 was added gene: RAB3GAP2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: RAB3GAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB3GAP2 were set to 24482476 Phenotypes for gene: RAB3GAP2 were set to spastic paraplegia Penetrance for gene: RAB3GAP2 were set to unknown Review for gene: RAB3GAP2 was set to RED Added comment: Described as a candidate HSP gene: Novarino (2014, 24482476) single account. Diagnostic on Sheffield HSP panel. Sources: Literature |
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Hereditary spastic paraplegia v1.71 | LYST |
Chris Buxton gene: LYST was added gene: LYST was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LYST were set to 24521565 Phenotypes for gene: LYST were set to spastic paraplegia Penetrance for gene: LYST were set to unknown Added comment: Shimazaki (2014, 24521565), homozygous LYST (c.4189T>G, p.F1397V). Gene predominantly associated with Chediak-Higashi syndrome. one publication describing a HSP like phenotype. Diagnostic on Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | KLC4 |
Chris Buxton gene: KLC4 was added gene: KLC4 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: KLC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KLC4 were set to 26423925 Phenotypes for gene: KLC4 were set to spastic paraplegia Penetrance for gene: KLC4 were set to Complete Review for gene: KLC4 was set to RED Added comment: Bayrakli (2015, 26423925). Affected, homozygous fs in three individuals in the same family. One family, limited evidence Diagnostic on Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | GCH1 |
Chris Buxton gene: GCH1 was added gene: GCH1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: GCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GCH1 were set to 24509643; 21935284 Phenotypes for gene: GCH1 were set to Dystonia; Spastic paraplegia Penetrance for gene: GCH1 were set to unknown Review for gene: GCH1 was set to GREEN Added comment: Fan (2014, 24509643) het for nonsense variant previously associated with dopa-responsive dystonia. Authors observe that Dopa-responsive Dystonia can resemble HSP Lee (2011, 21935284), another example of DRD misdiagnosed as Cerebral palsy with GCH1 c.1A>T; p.Met1Leu missense Diagnostic on Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | FARS2 |
Chris Buxton gene: FARS2 was added gene: FARS2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FARS2 were set to spastic paraplegia Penetrance for gene: FARS2 were set to unknown Review for gene: FARS2 was set to GREEN Added comment: Sahai (2018, 30250868) FARS2 cpd hhet with pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Biochemical evalutatoin showed impacts on activity of impacted enzyme . Yang (2016, 26553276), FARS cpd het on exome study, functional studies supportive. Phenotype is Spastic Paraplegia. Vantroys (2017, 29126765) writes that FARS can be associated with (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype. Descroibes 2 probands with phenotype including spasticity with cpd het varaints in FARs Sources: Literature |
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Hereditary spastic paraplegia v1.71 | CYP27A1 |
Chris Buxton gene: CYP27A1 was added gene: CYP27A1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYP27A1 were set to 25862734 Phenotypes for gene: CYP27A1 were set to progressive lower extremity spasticity,often disproportionate to any degree of weakness Penetrance for gene: CYP27A1 were set to unknown Review for gene: CYP27A1 was set to AMBER Added comment: Nicholls (2015, 25862734) Cerebrotendinous xanthomatosis AR disorder of bile acid metabolism can mimic more common conditions such as hereditary spastic paraparesis, or MS particularly if the phenotype is spinal xanthomatosis where the disease causes a spastic paraplegia Associated with rased cholestanol. paper describes homozygous, previously reported CYP27A1 variant, c.1183C>T, p.Arg395Trp (R395W) Diagnostic on Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | ARG1 |
Chris Buxton gene: ARG1 was added gene: ARG1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARG1 were set to 26310552; 23859858 Phenotypes for gene: ARG1 were set to Argininaemia; Progressive spastic tetraplegia Penetrance for gene: ARG1 were set to unknown Added comment: Spastic tetraplegia noted with ARG1 deficiency argininemia in neonates. Symptoms similar to cerebeal palsy so Dx is delayed Wu (2015, 26310552) identified 9 ARG1 varaints in 7 patients. Wu (2013, 23859858), similar paper to the above one. Progressive spastic tetraplegia, poor physical growth from 1 month to 4 years. When argininemia was found at the ages of 4 to 12 years, four of patients had mental retardation, and three had seizures. 6 ARG1 mutations identified. On Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | REEP2 | Chris Buxton reviewed gene: REEP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28491902; Phenotypes: spastic paprplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | MAG |
Chris Buxton gene: MAG was added gene: MAG was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MAG were set to spastic paprplegia Penetrance for gene: MAG were set to unknown Review for gene: MAG was set to RED Added comment: 1 family Novarino (2014, 24482476). Homozygous Cys430Gly with HSp phenotype. No other detail. 1 family. Limited evidence Diagnostic on Sheffield HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | KDM5C |
Chris Buxton gene: KDM5C was added gene: KDM5C was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: KDM5C was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: KDM5C were set to 10982473; 15586325; 26919706 Phenotypes for gene: KDM5C were set to Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism Penetrance for gene: KDM5C were set to unknown Review for gene: KDM5C was set to RED Added comment: Claes (2000, 10982473) reported candidate HSP locus Xp21.1-Xq21.3. Jensen (2005, 15586325) identified as JARID1C(syn)/KDM5C gene: c.2191C>T Leu731Phe. 4 males in same pedigree: two generations present with severe MR, slowly progressive spastic paraplegia, facial hypotonia, and maxillary hypoplasia. Additional features are aggressive behavior and strabismus; Fujita (2016, 26919706). Two different fs deletion variants. maternal reversion mechanims? Progressive spasticity component to phenotype. Currently diagnostic on Sheffield's HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | IBA57 |
Chris Buxton gene: IBA57 was added gene: IBA57 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IBA57 were set to 25609768 Phenotypes for gene: IBA57 were set to spastic paraplegia Penetrance for gene: IBA57 were set to unknown Review for gene: IBA57 was set to RED Added comment: Lossos (2015, 25609768). Homozygous donor splice-site mutation in the IBA57. mRNA studies done, some protein studies support pathogenicity. 1 family, limited evidence. Sources: Literature |
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Hereditary spastic paraplegia v1.71 | ABCD1 |
Chris Buxton gene: ABCD1 was added gene: ABCD1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: ABCD1 were set to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation Penetrance for gene: ABCD1 were set to unknown Review for gene: ABCD1 was set to GREEN Added comment: Guimarães (2001, 11810273), X-linked adrenoleukodystrophy. Spastic paraparesis with neurophysiologic abnormalities with an altered spinal cord MRI and a normal cerebral MRI. 2 different splice variants described Balicza (2016, 27084228), hereditary spastic paraplegia phenotype Spastic paraparesis; c.1553G>C p.R518P (no details) O'Neill (2001, 11739809), X-linked dominant hereditary spastic paraparesis Obligate female carriers affected, deletion 26 bp nt. 369-394, 5'UTR-cd.3 Koutsis (2015, 26049658) progressive spastic paraplegia with raised VLCFA, ABCD1 (c.1174_1178del, p.Leu392Serfs*7) Gene is on Sheffield's HSP panel Sources: Literature |
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Hereditary spastic paraplegia v1.71 | WDR48 | Chris Buxton reviewed gene: WDR48: Rating: RED; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Early onset spastic paraparesis, mild intellectual disability, kyphosis, pectus carinatum, hypertrichosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | TFG | Chris Buxton reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: None; Publications: 23479643, 27492651, 27601211; Phenotypes: spastic paraplegia, optic atrophy, neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | MTPAP | Chris Buxton reviewed gene: MTPAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20970105, 25008111, 27391121; Phenotypes: cerebellar ataxia, spastic paraparesis, dysarthria, optic atrophy, learning difficulties; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | MARS2 | Chris Buxton reviewed gene: MARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22448145; Phenotypes: Spastic Ataxia, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | GAD1 | Chris Buxton reviewed gene: GAD1: Rating: RED; Mode of pathogenicity: None; Publications: 15571623; Phenotypes: Cerebral palsy, spastic, symmetric; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | ENTPD1 | Chris Buxton reviewed gene: ENTPD1: Rating: RED; Mode of pathogenicity: None; Publications: 29691679, 24482476; Phenotypes: cognitive delay, spastic paraplegia, dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | AMPD2 | Chris Buxton reviewed gene: AMPD2: Rating: RED; Mode of pathogenicity: None; Publications: 24482476; Phenotypes: spastic paprplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | NT5C2 | Chris Buxton reviewed gene: NT5C2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28884889, 28327087, 29123918; Phenotypes: spastic paraplegia, mental retardation, Thin Corpus Callosum associated HSP; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | KIF1C | Chris Buxton reviewed gene: KIF1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 24482476, 24319291, 24482476, 17273843; Phenotypes: cerebellar ataxia, dysarthria, variable spasticity of the lower limbs, Cognition is not affected; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | ARL6IP1 | Chris Buxton reviewed gene: ARL6IP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28471035, 24482476; Phenotypes: spastic paraplegia, sensory and motor polyneuropathy, congenital insensitivity to pain, acromutilation, spastic paraplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.71 | ERLIN1 |
Alistair Pagnamenta gene: ERLIN1 was added gene: ERLIN1 was added to Hereditary spastic paraplegia. Sources: Other Mode of inheritance for gene: ERLIN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERLIN1 were set to PMID: 24482476 Phenotypes for gene: ERLIN1 were set to Hereditary spastic paraplegia Penetrance for gene: ERLIN1 were set to unknown Review for gene: ERLIN1 was set to GREEN Added comment: Sources: Other |
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Hereditary spastic paraplegia v1.71 |
Ellen McDonagh Panel name changed from Hereditary spastic paraplegia - childhood onset to Hereditary spastic paraplegia List of related panels changed from Hereditary spastic paraplegia to Panel types changed to Rare Disease 100K |
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Hereditary spastic paraplegia v1.70 | Ellen McDonagh Panel name changed from Hereditary spastic paraplegia to Hereditary spastic paraplegia - childhood onset | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.69 | Ellen McDonagh List of related panels changed from to Hereditary spastic paraplegia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hereditary spastic paraplegia v1.66 | SLC1A4 |
Louise Daugherty gene: SLC1A4 was added gene: SLC1A4 was added to Hereditary spastic paraplegia. Sources: Expert Review Mode of inheritance for gene: SLC1A4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC1A4 were set to 29989513; 27193218; 26138499; 26041762; 25930971 Phenotypes for gene: SLC1A4 were set to Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, 616657 Review for gene: SLC1A4 was set to GREEN Added comment: From review left on the Genetic Epilepsy Syndromes panel by Zornitza Stark (Australian Genomics) 4 Sep 2018, 3:29 a.m. Multiple affected individuals reported in the literature, seizures/EE are part of the phenotype. While initial reports identified a recurrent missense variant in individuals of Ashkenazi Jewish ancestry, there have been more recent reports of individuals from other ethnic backgrounds with different variants. Genomics England clinical team also thought the gene was relevant to the Hereditary spastic paraplegia. Sources: Expert Review |