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

M. Tariq, T. N. Khan, L. Lundin, M. Jameel, T. Lönnerholm, S. M. Baig, N. Dahl, J. Klar

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)182-186
Number of pages5
JournalClinical Genetics
Issue number1
Publication statusPublished - Jan 2018
Externally publishedYes


  • COMP
  • exome sequencing
  • homozygous
  • variant


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