• Alvera Vorster, Peter Beighton, Manogari Chetty, Yasmeen Ganie, Bertram Henderson, Engela Honey, Piet Maré, David Thompson, Karen Fieggen, Denis Viljoen, and Rajkumar Ramesar.
• MRC Human Genetics Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa. alvannvor@gmail.com.
• S. Afr. Med. J. 2017 Apr 25; 107 (5): 457-462.

BackgroundA relatively high frequency of autosomal recessively inherited osteogenesis imperfecta (OI) type 3 (OI-3) is present in the indigenous black southern African population. Affected persons may be severely handicapped as a result of frequent fractures, progressive deformity of the tubular bones and spinal malalignment.ObjectiveTo delineate the molecular basis for the condition.MethodsMolecular investigations were performed on 91 affected persons from seven diverse ethnolinguistic groups in this population.ResultsFollowing polymerase chain reaction amplification and direct cycle sequencing, FKBP10 mutations were identified in 45.1% (41/91) OI-3-affected persons. The homozygous FKBP10 c.831dupC frameshift mutation was confirmed in 35 affected individuals in the study cohort. Haplotype analysis suggests that this mutation is identical among these OI-3-affected persons by descent, thereby confirming that they had a common ancestor. Compound heterozygosity of this founder mutation was observed, in combination with three different deleterious FKBP10 mutations, in six additional persons in the cohort. Four of these individuals had the c.831delC mutation.ConclusionThe burden of the disorder, both in frequency and severity, warrants the establishment of a dedicated service for molecular diagnostic confirmation and genetic management of persons and families with OI in southern Africa.

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