Exome sequencing revealed a novel homozygous splice site variant in WNT1 gene underlying osteogenesis imperfecta type 3.

Exome sequencing revealed a novel homozygous splice site variant in WNT1 gene underlying osteogenesis imperfecta type 3.

Pediatr Res. 2017 Jun 30;:

Authors: Umair M, Alhaddad B, Rafique A, Jan A, Haack TB, Graf E, Ullah A, Ahmad F, Strom TM, Meitinger T, Ahmad W

Abstract BACKGROUND: Osteogenesis Imperfecta (OI) is a heritable bone fragility disorder usually caused by dominant variants in COL1A1 or COL1A2 genes. Over the last few years, seventeen genes including twelve autosomal recessive and five autosomal dominant forms of OI, involved in various aspects of bone formation, have been identified. METHODS: Whole exome sequencing followed by conventional Sanger sequencing was performed in single affected individual IV-3 in the present family. RESULTS: Here, we report clinical and genetic characterization of osteogenesis imperfecta type 3 in a consanguineous family with four affected members. Clinical examinations revealed low bone density, short stature, severe vertebral compression fractures, and multiple long bone fractures in the affected members. Exome sequencing revealed a biallelic pathogenic splice acceptor site variant (c.359-3C>G) in a wingless-type MMTV integration site family 1 (WNT1) gene located on chromosome 12q13.12. CONCLUSION: We report a biallelic splice site variant underlie osteogenesis imperfecta type 3 and the first case from Pakistani population.Pediatric Research accepted article preview online, 30 June 2017. doi:10.1038/pr.2017.149.

PMID: 28665926 [PubMed - as supplied by publisher]