• G Agenbag, A Vorster, S Julius, R Ramesar, and P Beighton.
• Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa. gloudi.agenbag@uct.ac.za.
• S. Afr. Med. J. 2020 Dec 14; 111 (1): 57-60.

BackgroundNamaqualand hip dysplasia (NHD) is a mild form of spondyloepiphyseal dysplasia in which progressive arthropathy of the hip joint is a major manifestation. The disorder was documented in a multigenerational South African (SA) family with antecedents from Namaqualand, a region in the north-west of the country. Linkage analysis revealed a locus that includes the collagen type II gene, COL2A1.ObjectivesTo identify the pathogenic COL2A1 variant causing NHD in an SA family.MethodsOne affected male with a clear diagnosis of NHD was selected for whole-exome sequencing (WES) on the Ion Torrent Proton platform. A probe-based assay and direct cycle sequencing were used to confirm that the prioritised variant segregated with the phenotype in the NHD family and was not present in unrelated controls from the same population.ResultsWES identified one heterozygous variant, c.2014G>T; p.(Gly672Cys), in the coding sequence of the COL2A1 gene. The variant segregated with NHD in 23 affected family members and was previously reported in a Caucasian male with Perthes disease-like presentation.ConclusionsIt is now possible to provide a molecular diagnosis of NHD before hip problems present. The large, clinically well-characterised NHD family is a valuable resource that could provide more insight into the mechanisms responsible for the variable expression observed in individuals with this variant.

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