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Limb disorders v1.126 | FAM92A |
Eleanor Williams changed review comment from: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. By exome sequencing they identified a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene in one child. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri.; to: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A with a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. It was confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. |
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Limb disorders v1.126 | FAM92A |
Eleanor Williams changed review comment from: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. Blood was taken from 3 affected and 3 non-affected idividuals. DNA from one child was used for exome sequencing and revealed a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), identified homozygosity for a nonsense mutation in the FAM92A gene (R160X; 617273.0001) that segregated with disease and was not found in 186 Pakistani controls. ▼ Animal Model Schrauwen et al. (2018) generated Fam92a -/- mice and observed extra bone growth or exostosis on the deltoid tuberosity of the humerus, consistent with tendon calcification. Abnormal digit morphology was significantly enriched in the mutant mice compared to controls, and included polysyndactyly and osteomas; to: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. By exome sequencing they identified a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene in one child. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. |
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Limb disorders v1.53 | FAM92A | Eleanor Williams Classified gene: FAM92A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Limb disorders v1.53 | FAM92A | Eleanor Williams Added comment: Comment on list classification: Promoted from red to amber. 1 case plus a mouse knockout showing a similar phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Limb disorders v1.53 | FAM92A | Eleanor Williams Gene: fam92a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Limb disorders v1.52 | FAM92A |
Eleanor Williams commented on gene: FAM92A: Provisionally associated with ?Polydactyly, postaxial, type A9 (#618219) in OMIM. PMID: 30395363 - Schrauwen et al. 2018 - 1 case. They report a consanguineous Pakistani family with 3 children with autosomal recessive nonsyndromic postaxial polydactyly type A. Blood was taken from 3 affected and 3 non-affected idividuals. DNA from one child was used for exome sequencing and revealed a homozygous nonsense variant (NM_001283034.1:c.478C>T, NP_001269963.1: p.[Arg160*]) in the FAM92A gene. Sanger sequencing confirmed that this variant segregates with PAPA. The c.478C>T variant (rs368652620) was observed in the gnomAD database with a very low MAF in the exome data (all populations MAF=2.04×10−5, South East Asians MAF=6.55×10−5 and no homozygous individuals observed and ) and was also not present in Sanger sequence data from 186 in-house control Pakistani DNAs. It is predicted to be targeted by the classical nonsense-mediated decay pathway. In mouse studies, FAM92A is expressed in the developing mouse limb and Fam92a−/− homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), identified homozygosity for a nonsense mutation in the FAM92A gene (R160X; 617273.0001) that segregated with disease and was not found in 186 Pakistani controls. ▼ Animal Model Schrauwen et al. (2018) generated Fam92a -/- mice and observed extra bone growth or exostosis on the deltoid tuberosity of the humerus, consistent with tendon calcification. Abnormal digit morphology was significantly enriched in the mutant mice compared to controls, and included polysyndactyly and osteomas |
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Limb disorders v1.47 | FAM92A |
Eleanor Williams gene: FAM92A was added gene: FAM92A was added to Limb disorders. Sources: Literature Mode of inheritance for gene: FAM92A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM92A were set to 30395363 Phenotypes for gene: FAM92A were set to postaxial polydactyly type A9 Review for gene: FAM92A was set to AMBER Added comment: Sources: Literature |