Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arthrogryposis v5.22 | LGI3 |
Achchuthan Shanmugasundram changed review comment from: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons. This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype. Sources: Literature; to: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons. This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v5.21 | LGI3 |
Achchuthan Shanmugasundram gene: LGI3 was added gene: LGI3 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: LGI3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LGI3 were set to 35948005 Phenotypes for gene: LGI3 were set to Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007 Review for gene: LGI3 was set to GREEN Added comment: PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability. Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability. Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons. This gene has been associated with relevant phenotype in OMIM (MIM #620007), but not yet in Gene2Phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v5.17 | ACTC1 | Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (five unrelated families) available in support of the association of ACTC1 with distal arthrogryposis and hence this gene can be promoted to green rating in the next GMS review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v5.16 | ACTC1 |
Achchuthan Shanmugasundram gene: ACTC1 was added gene: ACTC1 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACTC1 were set to 37457373 Phenotypes for gene: ACTC1 were set to distal arthrogryposis, MONDO:0019942 Review for gene: ACTC1 was set to GREEN Added comment: Eight individuals from five unrelated families were identified with five different heterozygous missense variants in ACTC1 gene and they were reported with distal arthrogryposis. The clinical presentations included multiple congenital contractures, neck pterygia, scoliosis, and congenital heart defects/cardiomyopathy, short stature. This gene has been associated with cardiac phenotypes in both OMIM and Gene2Phenotype, but not yet with distal arthrogryposis in either resources. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v5.10 | FILIP1 |
Achchuthan Shanmugasundram changed review comment from: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis with contractures of the knees and elbows, congenital clubfoot, muscular hypotonia, and mild learning disability. PMID:36943452 reported five individuals from three unrelated families with three different biallelic variants in FILIP1 gene (including the variant reported in the patient from PMID:36344539) and presenting with an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism.; to: PMID:36344539 reported a single male with biallelic variant in FILIP1 (c.2665C > T/ p.Arg889Ter) gene and presenting with distal arthrogryposis with contractures of the knees and elbows, congenital clubfoot, muscular hypotonia, and mild learning disability. PMID:36943452 reported five individuals from three unrelated families with three different biallelic variants in FILIP1 gene (including the variant reported in the patient from PMID:36344539) and presenting with an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism. PMID:37163662 reported five individuals from four unrelated families with four different biallelic variants, out of which three individuals from two different families presented with congenital onset of contractures. This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v5.2 | COL25A1 |
Achchuthan Shanmugasundram gene: COL25A1 was added gene: COL25A1 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: COL25A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COL25A1 were set to 35077597 Phenotypes for gene: COL25A1 were set to Arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder Review for gene: COL25A1 was set to GREEN Added comment: PMID:35077597 reported five patients from three unrelated families identified with biallelic variants in COL25A1 gene presented with a phenotype characterized by arthrogryposis with or without an ocular congenital cranial dysinnervation disorder. The severity of arthrogryposis varied, ranging from mild distal upper limb involvement to arthrogryposis multiplex congenita. Although the extraocular muscle phenotype has been reported in OMIM (MIM # 616219) and Gene2Phenotype, arthrogryposis has not yet been included in these records. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v4.12 | SELENON | Achchuthan Shanmugasundram Phenotypes for gene: SELENON were changed from Muscular dystrophy, rigid spine, 1, 602771; Myopathy, congenital, with fiber-type disproportion 255310 to Congenital myopathy 3 with rigid spine, OMIM:602771 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v4.9 | CAMLG |
Achchuthan Shanmugasundram gene: CAMLG was added gene: CAMLG was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAMLG were set to 35262690 Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation, type IIz, OMIM:620201 Review for gene: CAMLG was set to RED Added comment: Comment on classification of gene: This gene should be rated red as there is only one patient reported so far. PMID:35262690 reported one patient with homozygous c.633 + 4A>G splice variant in CAMLG presented with a predominantly neurological phenotype with psychomotor disability, contractures, epilepsy, hypotonia and brain malformations. This gene has already been associated with phenotype in OMIM (MIM #620201), but not in Gene2Phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.162 | ADAMTS15 |
Sarah Leigh gene: ADAMTS15 was added gene: ADAMTS15 was added to Arthrogryposis. Sources: Literature Q3_22_rating, Q3_22_MOI tags were added to gene: ADAMTS15. Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADAMTS15 were set to 35962790 Phenotypes for gene: ADAMTS15 were set to distal arthrogryposis Review for gene: ADAMTS15 was set to GREEN Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least four variants have been reported by PMID: 35962790 in four independent consanguineous families, the unaffected parents were heterozgous for the causative variants in each of the families. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.159 | KIF26B | Arina Puzriakova Added comment: Comment on list classification: Rating Red as only a single case (PMID: 30151950) has been reported to this date. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.157 | PEX6 | Sarah Leigh edited their review of gene: PEX6: Added comment: Arthrogryposis maybe over looked in patients with Peroxisome biogenesis disorder 4A (Zellweger) (OMIM:614862) and Peroxisome biogenesis disorder 4B (OMIM:6148630), as these conditions are characterized by a severe phenotype and premature death in some cases. If this is the case, for Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) have identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).; Changed mode of pathogenicity: Other; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.147 | KIF26B |
Zornitza Stark gene: KIF26B was added gene: KIF26B was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: KIF26B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF26B were set to 30151950 Phenotypes for gene: KIF26B were set to Progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis Review for gene: KIF26B was set to RED Added comment: 1 report only of infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. Whole exome sequencing on the trio identified a de novo KIF26B missense variant (p.Gly546Ser). Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.140 | DMPK |
Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK. Tag currently-ngs-unreportable tag was added to gene: DMPK. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.128 | ERGIC1 | Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote this gene to Green at the next GMS panel update - three unrelated families reported to date with arthrogryposis associated with different variants in this gene (PMID: 28317099; 31230720; 34037256). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.125 | SLC29A3 | Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lucy Jackson (NHS). Fixed flexion contractures of the fingers, toes and elbows have been reported in FHC and H-syndrome. Sufficient unrelated cases of joint contractures which can be a presenting feature to rate as Green at the next GMS panel update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.122 | ERGIC1 |
Zornitza Stark gene: ERGIC1 was added gene: ERGIC1 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERGIC1 were set to 28317099; 34037256 Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100 Review for gene: ERGIC1 was set to AMBER Added comment: Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.120 | CNTN1 | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber as two families with homozygous variants and a relevant phenotype have now been reported in literature. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.113 | MYOD1 | Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics) on Congenital myopathy panel. This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is currently not enough evidence to support a gene-disease association on this panel (Arthrogryposis). Therefore, this gene has been given an Amber rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.108 | FLNA | Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant disorder on OMIM and G2P. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.107 | ACTA1 | Ivone Leong Phenotypes for gene: ACTA1 were changed from Nemaline myopathy 3, autosomal dominant or recessive 161800; Myopathy, actin, congenital, with excess of thin myofilaments 161800; Myopathy, actin, congenital, with cores 161800; nemaline myopathy; Nemaline myopathy 3, autosomal dominant or recessive, 161800Myopathy, actin, congenital, with excess of thin myofilaments, 161800Myopathy, actin, congenital, with cores, 161800Myopathy, congenital, with fiber-type disproportion 1, 255310; Nemaline Myopathy; CMD with rigid spine to Myopathy, actin, congenital, with cores, OMIM:161800; Myopathy, actin, congenital, with excess of thin myofilaments, OMIM:161800; Myopathy, congenital, with fiber-type disproportion 1, OMIM:255310; Nemaline myopathy 3, autosomal dominant or recessive, OMIM:161800; CMD with rigid spine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.101 | ISLR2 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. Single family reported in PMID: 30483960 with congenital hydrocephalus, arthrogryposis and abdominal distension and a homozygous a frameshift deletion that segregated with disease. Knockout mouse model recapitulates some features of the human phenotype, i.e. hydrocephalus (PMID: 29739947). Rating Red, awaiting further cases. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.98 | ERBB3 | Sarah Leigh edited their review of gene: ERBB3: Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene for Lethal congenital contractural syndrome 2 OMIM:607598 and as a confirmed gene for Hirschprung disease with intestinal pseudo-obstruction. At least 7 variants reported in at least 4 unrelated cases.; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.90 | UNC50 | Arina Puzriakova Added comment: Comment on list classification: Rating Red awaiting further evidence. Only a single variant described in 2 individuals (PMIDs: 29016857; 33820833). Additional cases with different variants or strong functional support required to validate pathogenicity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.88 | UNC50 |
Arina Puzriakova gene: UNC50 was added gene: UNC50 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: UNC50 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC50 were set to 29016857; 33820833 Phenotypes for gene: UNC50 were set to Arthrogryposis multiplex congenita Review for gene: UNC50 was set to AMBER Added comment: UNC50 is currently not associated with any phenotype in OMIM (last edited on 02/01/2018) or Gene2Phenotype. - PMID: 29016857 (2017) - Homozygosity mapping of disease loci combined with WES in a single male from a consanguineous family presenting with lethal AMC revealed a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4). Functional studies in C. elegans showed the variant caused loss of acetylcholine receptor expression in the muscle. - PMID: 33820833 (2021) - Single individual reported with the same homozygous c.750_751del:p.Cys251Phefs*4 variant in UNC50 as previously described. The case was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and tetra ventricular dilation were detected prenatally. -- Note: it isn't definitively clear whether these are different individuals. Both are singleton males born to consanguineous parents, with the same variant and similar phenotype. Also both infants died at 28 w.g. However, the 2021 paper (PMID:33820833) states their patient was selected from a cohort of cases without a molecular diagnosis and indicate the UNC50 gene had already previously been identified in relation to this phenotype, highlighting the earlier paper (PMID:29016857). There is also no mention of tetra ventricular dilation in the first case, so it is likely that these do represent distinct individuals. Additional cases needed to provide clarity. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.76 | ADCY6 | Arina Puzriakova edited their review of gene: ADCY6: Added comment: - PMID: 33820833 (2021) - Further 2 sibs reported with a homozygous c.3346C>T:p.Arg1116Cys variant in the ADCY6 gene. The family was identified from a cohort of 315 genetically undiagnosed and unrelated AMC families. Arthrogryposis and IUGR were detected prenatally.; Changed rating: GREEN; Changed publications: 24319099, 26257172, 31846058, 33820833; Changed phenotypes: Lethal congenital contracture syndrome 8, OMIM:616287; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.76 | KIDINS220 | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but with the recommendation of a green rating following GMS review. 3 cases reported plus a supportive mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.75 | KIDINS220 |
Eleanor Williams gene: KIDINS220 was added gene: KIDINS220 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: KIDINS220 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIDINS220 were set to 32909676; 33205811; 28934391; 22048169 Phenotypes for gene: KIDINS220 were set to brain ventriculomegaly and limb contractures Review for gene: KIDINS220 was set to GREEN Added comment: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases. 3 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap: PMID: 32909676 - El-Dessouky et al 2020 - report a consanguineous family of Egyptian origin with several miscarriages. Prenatal ultrasonography revealed limb contractions and ventriculomegaly aswell as cerebellar anomalies, cardiac anomalies and hydrops fetalis. Using WES a homozygous deleterious frameshift variant (c.208del; p.Asp70Ilefs*18) in KIDINS220 gene was identified. Both parents were heterozygous for this variant. PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation. PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein. PMID: 22048169 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.73 | MYLPF | Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that in view of only 2 families with arthrogryposis and monoallelic variants in this gene there is currently not enough evidence to support inclusion of the monoallelic form. More cases or a delineation of the mechanism of pathogenicity are required before considering adding this as an MOI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.59 | MYH2 | Arina Puzriakova Added comment: Comment on mode of inheritance: Independent reports of both biallelic (PMIDs: 20418530; 24193343) and monoallelic cases (PMIDs: 23489661) with joint contractures. MOI should therefore be changed from 'Monoallelic' to 'Both monoallelic and biallelic' at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.45 | NEK9 | Arina Puzriakova Added comment: Comment on list classification: With addition of the recent report, there are now at least 3 unrelated families presenting arthrogryposis and different biallelic variants in this gene. This now reaches threshold for inclusion, and therefore NEK9 should be promoted to Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.44 | NEK9 |
Arina Puzriakova edited their review of gene: NEK9: Added comment: Deden et al. 2020 (PMID: 32333414) report a further family with two consecutive prenatal presentations with compound heterozygous NEK9 variants. Both fetuses had arthrogryposis. Both variants were reported as VUS when detected in the first fetus, which initially presented with 'short long bones, bowed femur, micrognathia, talipes and deviated hand' but re-evaluated after the phenotype progressed to arthrogryposis and then the next pregnancy showed the same ultrasound abnormalities and the same compound het variants. At this point the authors felt this represented a conclusive diagnosis.; Changed rating: GREEN; Changed publications: 26908619, 21271645, 26633546, 32333414; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.44 | ATP1A2 |
Arina Puzriakova Added comment: Comment on list classification: Two additional unrelated families reported by Chatron et al PMID: 31608932 with affected fetuses described as having polymicrogyria, microcephaly, polyhydramnios and FADS. Two individuals from one family also presented hand contractures and rocker-bottom feet, bringing the total to 3 unrelated families with relevant phenotype. As number of cases now reaches threshold for inclusion as diagnostic-grade, ATP1A2 should be promoted to Green at the next GMS panel update (added 'for-review' tag) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.41 | FLNC | Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber, but should be promoted to Green at the next GMS panel update (added 'for-review' tag). PMID: 29858533 reports on 3 unrelated individuals who presented at birth with arthrogryposis. This was evident prior to other FLNC-related features such as muscle weakness and cardiomyopathy, and so it is plausible that these cases may be tested in the context of this clinical indication. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.36 | TBCD | Arina Puzriakova Added comment: Comment on list classification: Maintaining the Red rating on this panel as curation of published literature revealed only a single report of an individual with multiple arthrogryposis (individual II-2 from PMID:27666374). This disorder is better represented by other panels for which this gene is already Green (Genetic epilepsy syndromes, Intellectual disability, etc). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.31 | SCYL2 | Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). 2 unrelated families reported at present with different SCYL2 variants and a syndromic form of severe AMC comprising microcephaly, absent corpus callosum, optic atrophy, limb fractures, profound GDD, and early lethality. Rating Amber as additional cases required before inclusion on a diagnostic panel (added 'watchlist' tag). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.27 | TOR1AIP1 | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag). Joint contractures observed in at least 4/6 families reported to date (when considering 5 kindreds with same founder variant collectively). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.18 | SCN1A |
Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases (4) reported in 2 papers (PMIDs: 32928894 and 29543227) with ACM and variants in this gene. It is anticipated that early-onset seizures likely represent the predominant feature of the disease presentation (already Green on the Genetic epilepsy syndromes panel), however this gene will be flagged for review to assess whether inclusion on this panel is likely to be of clinical benefit. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.13 | SCN1A |
Arina Puzriakova changed review comment from: Comment on list classification: Association with this phenotype currently based on a single publication, although reporting 3 unrelated cases. Rating Amber, awaiting further publications/clinical evidence to validate this gene-disease association.; to: Comment on list classification: Association with this phenotype currently based on a single publication, although reporting 3 unrelated cases. Rating Amber, awaiting further publications/clinical evidence to validate this gene-disease relationship. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.13 | SCN1A |
Arina Puzriakova Added comment: Comment on list classification: Association with this phenotype currently based on a single publication, although reporting 3 unrelated cases. Rating Amber, awaiting further publications/clinical evidence to validate this gene-disease association. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.11 | MYLPF |
Zornitza Stark gene: MYLPF was added gene: MYLPF was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLPF were set to 32707087 Phenotypes for gene: MYLPF were set to Distal arthrogryoposis Review for gene: MYLPF was set to AMBER Added comment: 2 different homozygous variants reported in 6 consanguineous families with DA and an additional 2 different dominantly inherited variants in 2 families, with supporting animal model. Overall neither MOI data sufficient for Green rating. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.11 | NUP88 |
Zornitza Stark gene: NUP88 was added gene: NUP88 was added to Arthrogryposis. Sources: Expert list Mode of inheritance for gene: NUP88 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP88 were set to 30543681 Phenotypes for gene: NUP88 were set to Fetal akinesia deformation sequence 4, MIM# 618393 Review for gene: NUP88 was set to GREEN gene: NUP88 was marked as current diagnostic Added comment: Two unrelated families, functional data on the variants support pathogenicity as does a zebrafish model. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.11 | ERCC5 | Zornitza Stark changed review comment from: Single family reported with 5 affected fetuses and severe COFS including arthrogryposis.; to: A family reported with 5 affected fetuses and severe COFS including arthrogryposis in PMID:24700531. Further two included in a recent review of severe neonatal presentations of nucleotide excision-repair disorders (PMID:32557569). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.11 | EBP |
Zornitza Stark gene: EBP was added gene: EBP was added to Arthrogryposis. Sources: Expert list Mode of inheritance for gene: EBP was set to Other Publications for gene: EBP were set to 21634086; 24704792 Phenotypes for gene: EBP were set to Chondrodysplasia punctata, X-linked dominant, MIM# 302960 Review for gene: EBP was set to GREEN gene: EBP was marked as current diagnostic Added comment: XLD. Contractures are a reported feature. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v3.11 | SCYL2 |
Zornitza Stark gene: SCYL2 was added gene: SCYL2 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCYL2 were set to 31960134; 26203146 Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita (AMC); Zain syndrome Review for gene: SCYL2 was set to AMBER Added comment: 2 unrelated consanguineous families reported with AMC. Constitutive mouse knockout of Scyl2 results in neonatal lethality and severe motor and sensory deficits. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.104 | BICD2 |
Zerin Hyder changed review comment from: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic women with subclinical findings with the previously described p.(Thr703Met) variant. PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure.; to: PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands. PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic woman with subclinical findings with the previously described p.(Thr703Met) variant. PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.100 | TOR1AIP1 | Rebecca Foulger Added comment: Comment on list classification: One family (PMID:24856141) supports a Red rating. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.99 | TOR1AIP1 |
Rebecca Foulger gene: TOR1AIP1 was added gene: TOR1AIP1 was added to Arthrogryposis. Sources: Literature,Other Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TOR1AIP1 were set to 24856141 Phenotypes for gene: TOR1AIP1 were set to joint contractures; ?Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, 617072 Added comment: Added TOR1AIP1 to panel based on Amber rating on R266 Neuromuscular arthrogryposis panel, and PMID:24856141 2014 paper who report a consanguineous Turkish family with muscle weakness, atrophy and joint contractures in three affected individuals (2 siblings and a cousin). They all had a homozygous variant in TOR1AIP1 (c.186delG causing a premature stop codon). Healthy parents were heterozygous carriers, and allele segregation in the family supported recessive inheritance. Sources: Literature, Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.98 | SLC18A3 | Rebecca Foulger Added comment: Comment on publications: PMID:27590285: report individuals from 2 families with biallelic SLC18A3 variants and presynaptic congenital myasthenic syndrome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger commented on gene: SLC18A3: PMID:28188302 (Aran et al., 2017) report 2 brothers from a nonconsanguineous Yemeni Jewish family manifested at birth with severe hypotonia and arthrogryposis. The brothers were homozygous for missense variant in SLC18A3 c.1078G>C, p.Gly360Arg. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.97 | SLC18A3 | Rebecca Foulger commented on gene: SLC18A3: PMID:31059209 (Hakonen et al., 2019) report 2 sibling Finnish fetuses with with fetal akinesia, arthrogryposis, edema, and partial cleft palate and a homozygous variant in SLC18A3: c.1116C>A, p.(Cys372Ter). The parents were distant relatives. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.96 | SLC18A3 |
Rebecca Foulger gene: SLC18A3 was added gene: SLC18A3 was added to Arthrogryposis. Sources: Other,Literature Mode of inheritance for gene: SLC18A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC18A3 were set to 28188302; 27590285; 31059209 Phenotypes for gene: SLC18A3 were set to Myasthenic syndrome, congenital, 21, presynaptic, 617239; arthrogryposis Added comment: Added to panel based on Amber rating on Neuromuscular arthrogryposis panel V0.21 and literature evidence supporting an Arthrogryposis phenotype. Sources: Other, Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.84 | DHCR24 | Zerin Hyder changed review comment from: Schaaf et al: one case with dermosterolsis with relative macrocephaly, mild arthrogryposis, and dysmorphic facial features. The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA. The patient was found to be a compound heterozygote for c.281G>A (p.R94H) and c.1438G>A (p.E480K) mutations. 4 individuals in Bedouin kindred with dermosterolsis and distal contractures. Two other reports 12457401; 29175559 in association with milder phenotype of AMC.; to: Schaaf et al: patient with dermosterolsis with relative macrocephaly, mild arthrogryposis, and dysmorphic facial features. The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA. The patient was found to be a compound heterozygote for c.281G>A (p.R94H) and c.1438G>A (p.E480K) mutations. 4 individuals in Bedouin kindred with dermosterolsis and distal contractures. Two other reports 12457401; 29175559 in association with milder phenotype of AMC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.84 | DPAGT1 |
Zerin Hyder changed review comment from: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome in 23447650; to: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Multiple joint contractures reported in association with congenital myaesthenic syndrome and DPAGT1 mutations. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.84 | DPAGT1 |
Zerin Hyder changed review comment from: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome.; to: Green gene on neuromuscular arthrogryposis panel. Ganetzky et al, 2015: Newborn female with arthrogryposis multiplex due to fetal akinesia. Transferrin isoelectric focusing was suggestive of a type I congenital disorder of glycosylation; sequencing revealed homozygous missense mutation in DPAGT1. Carrera et al: DPAGT1-CDG in patient with fetal hypokinesia and AMC. Contractures reported in association with congenital myaesthenic syndrome in 23447650 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.65 | MAGEL2 | Rebecca Foulger commented on gene: MAGEL2: G2P phenotype is 'ARTHROGRYPOSIS MULTIPLEX CONGENITA' with 'probable' disease confidence, in addition to 'Schaaf-Yang syndrome' with confirmed confidence. G2P rating based on PMID:26365340 who report 2 families with lethal arthrogryposis in deceased fetuses and MAGEL2 variant. PMID:27195816 (Fountain et al., 2017) identified the same heterozygous c.1996delC variant in 2 fetal siblings with Shaaf-Yang syndrome manifesting as AMC. PMID:31504653 (Gregory et al., 2019) report 5 patients (4 families), 3 of whom had arthrogryposis and the Gln666SerfsTer36 MAGEL2 variant. Additional papers reporting arthrogryposis as part of Schaaf-Yang syndrome E.g. PMID:29359444 so likely to be the same condition with variable severity/phenotype. Sufficient cases of arthrogryposis in the literature for a Green rating on Arthrogryposis panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.64 | SLC6A9 | Rebecca Foulger commented on gene: SLC6A9: Gene2Phenotype phenotype of 'Glycine Encephalopathy with Arthrogryposis' with 'probable' disease confidence based on PMID:27773429 (Kurolap et al., 2016) who report 4 individuals from 2 Arab-Muslim families with arthrogryposis amongst their symptoms. In addition, PMID:27481395 (Alfadhel et al., 2016) report a consanguineous family with one child who presented with non-ketotic hyperglycinemia and a homozygous missense variant in SLC6A9 (p.Ser407Gly). Features included joint laxity but Arthrogryposis isn't mentioned specifically. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.58 | STAC3 | Rebecca Foulger commented on gene: STAC3: Although the variants were originally only reported from the same population (Lumbee Indian tribe), PMID:28777491 (Telegrafi et al., 2017) report the W284S homozygous variant in a child born of consanguineous parents from Qatar, and in a compound het state in 2 siblings from Puerto Rico. This demonstrates that this variant is not restricted to the Native American population and I have therefore removed the 'founder-effect' tag. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.45 | SMPD4 | Louise Daugherty changed review comment from: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.; to: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.45 | SMPD4 | Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.40 | ASCC1 | Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.37 | ASCC1 |
Julia Baptista gene: ASCC1 was added gene: ASCC1 was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASCC1 were set to PMID: 26924529; 30327447; 28749478 Phenotypes for gene: ASCC1 were set to spinal muscular atrophy; arthrogryposis; fetal akinesia; hypotonia; contractures Review for gene: ASCC1 was set to GREEN gene: ASCC1 was marked as current diagnostic Added comment: Homozygous frameshift variant reported in two siblings from a Turkish family and one child from a Portuguese family affected with fetal akinesia, arthrogryposis, hypotonia, muscle weakness and congenital bone fractures. One further family reported with fetal akinesia and a homozygous splicing variant. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis v2.33 | COASY | Louise Daugherty Added comment: Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis | POR | Alice Gardham marked POR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis | POR | Alice Gardham added POR to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arthrogryposis | POR | Alice Gardham reviewed POR |