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

Tariq M, Khan TN, Lundin L, Jameel M, Lönnerholm T, Baig SM, Dahl N, Klar J

Clin. Genet. 93 (1) 182-186 [2018-01-00; online 2017-11-21]

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 2 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 2 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 2 mutated alleles.

Affiliated researcher

PubMed 28685811

DOI 10.1111/cge.13091

Crossref 10.1111/cge.13091


Publications 7.1.2