Homozygosity for a missense variant in COMP gene associated with severe pseudoachondroplasia.

Homozygosity for a missense variant in COMP gene associated with severe pseudoachondroplasia. Clin Genet. 2017 Jul 07;: Authors: Tariq M, Khan TN, Lundin L, Jameel M, Lönnerholm T, Baig SM, Dahl N, Klar J Abstract The phenotypic spectrum associated with heterozygous mutations in cartilage oligomeric matrix protein gene (COMP) range from a mild form of multiple epiphyseal dysplasia (MED) to pseudoachondroplasia (PSACH). However, the phenotypic effect from biallelic COMP variants is unclear. We investigated a large consanguineous Pakistani family with a severe form of PSACH in two individuals. Another 14 family members presented with a mild PSACH phenotype similar to MED. Using exome sequencing and subsequent segregation analysis, we identified homozygosity for a COMP missense variant (c.1423G>A; p.(D475N)) in the two severely affected individuals, whereas family members with the mild PSACH phenotype were heterozygous. Our observations show for the first time that a biallelic COMP variant may be associated with pronounced and widespread skeletal malformations suggesting an additive effect of the two mutated alleles. PMID: 28685811 [PubMed - as supplied by publisher]
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research