Case Report of Two Siblings Diagnosed with Osteogenesis Imperfecta Type XV with a New Mutation in the <em>WNT1</em> Gene and Review of the Literature

pubmed: wnt1 2023-06-01

Mol Syndromol. 2023 Apr;14(2):164-170. doi: 10.1159/000528201. Epub 2023 Jan 11.


INTRODUCTION: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fractures and low bone mass. Recently, mutations of the WNT1 gene have been reported to be causative in OI. The mutation in WNT1 causes autosomal-recessive OI due to its critical role in bone formation. WNT1 mutations cause varying degrees of clinical severity, ranging from moderate to progressively deforming forms. In addition to the OI phenotype, our cases also had extra-skeletal findings.

CASE PRESENTATION: We describe two siblings with multiple fractures and developmental delay. A novel homozygous frameshift WNT1 mutation was detected in this family, and we reviewed the literature for WNT1-related OI cases.

DISCUSSION: We report a novel variant with a clinical diagnosis of severe OI, and this review will provide a comprehensive overview of previously published cases of OI type XV. With a better understanding of disorders associated with WNT1 mutations, therapies targeting Wnt1 signaling pathway may contribute therapeutic benefits.

PMID:37064339 | PMC:PMC10091007 | DOI:10.1159/000528201