Type XV osteogenesis imperfecta: A novel mutation in the <em>WNT1</em> gene, c.620G &gt;A (p.R207H), is associated with an inner ear deformity

pubmed: wnt1 2023-06-01

Intractable Rare Dis Res. 2023 Feb;12(1):58-61. doi: 10.5582/irdr.2022.01099.


The Wnt signaling pathway is vital in encouraging bone growth. WNT1 gene mutations have been identified as the major cause of type XV osteogenesis imperfecta (OI). Described here is a case of complex heterozygous WNT1 c.620G>A (p.R207H) and c.677C >T (p.S226L) OI caused by a novel mutation at locus c.620G >A (p.R207H). The female patient had type XV OI, distinguished by poor bone density, frequent fractures, a small stature, skull softening, lack of dentine hypoplasia, a brain malformation, and obvious blue sclera. A CT scan of the temporal bone revealed abnormalities of the inner ear, necessitating a hearing aid 8 months after birth. There was no family history of such disorders in the proband's parents. The proband inherited complex heterozygous WNT1 gene variants c.677C>T (p.S226L) and c.620G>A (p.R207H) from her father and mother, respectively. Presented here is a case of OI with inner ear deformation caused by c.620G>A (p.R207H), which is a novel WNT1 site mutation. This case broadens the genetic spectrum of OI and it provides a rationale for genetic testing of mothers and a medical consultation to estimate the risk of fetal illness.

PMID:36873675 | PMC:PMC9976088 | DOI:10.5582/irdr.2022.01099