Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia. Issue 4 (10th February 2019)

• Record Type: Journal Article
• Authors: Dasa, Vinod; Eastwood, James R.B.; Podgorski, Michal; Park, Heewon; Blackstock, Christopher; Antoshchenko, Tetyana; Rogala, Piotr; Bieganski, Tadeusz; Jazwinski, S. Michal; Czarny‐Ratajczak, Malwina
• Is Part Of: American journal of medical genetics. Volume 179:Issue 4(2019)
• Page Start: 534
• Page End: 541
• Publication Date: 2019-02-10
• Subjects: double‐layered patella -- multiple epiphyseal dysplasia -- novel mutation in COL2A1; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61049
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.