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| Childhood onset hereditary spastic paraplegia v4.32 | ALK | Achchuthan Shanmugasundram Classified gene: ALK as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v4.32 | ALK | Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, PMID:32989326 reported a large cohort study of cerebral palsy, where two patients were identified with monoallelic ALK variants and presented with spastic diplegia with mild tremor or spastic-dystonic diplegia. Hence, this gene can be rated amber with current evidence. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v4.32 | ALK | Achchuthan Shanmugasundram Gene: alk has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v4.31 | ALK | Achchuthan Shanmugasundram reviewed gene: ALK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: spastic diplegia, MONDO:0001167; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v3.23 | RNF170 |
Achchuthan Shanmugasundram changed review comment from: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy. PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia. PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays.; to: PMID:31636353 reported 9 patients from 4 unrelated families with childhood-onset spastic paraplegia. The age of onset of the condition ranged from 2 to 5 years of age and they were all identified with a homozygous variant in RNF170 gene. It is a neurological disorder characterised by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities, with oilder patients also having upper limb involvement and axonal polyneuropathy. PMID:33165979 reported four members from a single family carrying a homozygous stop gain variant in RNF170 and diagnosed with hereditary spastic paraplegia. PMID:35041108 reported a 7 year old girl with novel homozygous missense variant in RNF170 and she presented with progressive difficulty in walking that started when she was 3 years old, lower limb predominant spastic paraparesis, and mild upper limbs involvement with slight tremor in the hands, all occurring in the absence of neurodevelopmental or growth delays. This gene has been associated with relevant phenotypes in OMIM (MIM #619686), but not yet in Gene2Phenotype. |
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| Childhood onset hereditary spastic paraplegia v2.151 | CTNNB1 |
Arina Puzriakova gene: CTNNB1 was added gene: CTNNB1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature Q4_22_promote_green tags were added to gene: CTNNB1. Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CTNNB1 were set to 23033978; 24614104; 25326669; 26968164; 27915094; 34321325 Phenotypes for gene: CTNNB1 were set to Neurodevelopmental disorder with spastic diplegia and visual defects, OMIM:615075 Review for gene: CTNNB1 was set to GREEN Added comment: Childhood-onset spasticity is a key feature of the neurodevelopmental phenotype caused by pathogenic monoallelic variants in the CTNNB1 gene. Over 15 unrelated cases reported in literature, almost all of which developed spasticity which significantly affected ability to walk. Sources: Literature |
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| Childhood onset hereditary spastic paraplegia v2.19 | ALK |
Zornitza Stark gene: ALK was added gene: ALK was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALK were set to 32989326 Phenotypes for gene: ALK were set to Spastic-dystonic diplegia Review for gene: ALK was set to AMBER Added comment: Variants in this gene are linked to susceptibility to neuroblastoma. PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient. Sources: Literature |
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| Childhood onset hereditary spastic paraplegia v2.13 | SARS2 |
Sarah Leigh gene: SARS2 was added gene: SARS2 was added to Hereditary spastic paraplegia - childhood onset. 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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| Childhood onset hereditary spastic paraplegia v1.68 | TFG |
Louise Daugherty commented on gene: TFG: Amber rating on Hereditary spastic paraplegia panel 1.198 Beetz (2013, 23479643) Initial report. Exome study, 2 sibs with early-onset spastic paraplegia, optic atrophy, and neuropathy, with hom c.316C>T (p.R106C). In vitro defect shown in self-assembly. Harlalka (2016, 27492651) also described a c.317G>A (p.R106H) homozygous family, and proposed a founder origin for the c.316C>T variant, as well as a c.316_317 hotspot. further mt invitro studies supportive evidence. Elsayed (2016, 27601211) implicated TGF in one family; homozygous c.64C>T (p.(Arg22Trp) with HSP In Sheffield diagnostic HSP panel Chris Buxton (North Bristol NHS Trust), 27 Nov 2018 Comment when marking as ready: Single Indian family currently described in association with HSP emma baple (Genomics England Curator), 10 May 2016 |
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| Childhood onset hereditary spastic paraplegia v1.65 | REEP2 |
Louise Daugherty commented on gene: REEP2: Amber rating on Hereditary spastic paraplegia panel 1.198 Roda (2017, 28491902). de novo REEP2 missense (c.119T > G, p.Met40Arg) at a highly-conserved residue very close to another known pathogenic missense change. No functional studies. Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Submitted Amber rating. Comment on list classification: changed from red to amber based on upon two families Louise Daugherty (Genomics England Curator), 30 Nov 2017 Known to be a movement disorder associated gene. Associated with phenotype in OMIM. At least 3 variants reported in 2 large unrelated families, Autosomal dominant inheritance was reported in one family and autosomal recessive inheritance in another. Observed clinical phenotype includes difficulty in walking and stiff legs associated with hyperreflexia and extensor plantar responses in early childhood. Cognition, speech, and ocular function are normal (summary by Esteves et al., PMID:24388663) Louise Daugherty (Genomics England Curator), 27 Nov 2017 |
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