Variants in GLI3 Cause Greig Cephalopolysyndactyly Syndrome.

Abstract

Background: Greig cephalopolysyndactyly syndrome (GCPS) is a disorder of autopod and craniofacial abnormalities. Autopod anomalies include preaxial and/or postaxial polydactyly together with or without syndactyly while craniofacial features include hypertelorism and macrocephaly. GCPS is inherited in an autosomal dominant manner and is caused by sequence variants in GLI3. Methodology and Results: In this study, we examined four unrelated families with GCPS segregating in an autosomal dominant manner. Sanger sequencing revealed three novel (p.Tyr146Leufs*19, p.Glu99Serfs*60, and p.Thr541Arg) and one previously reported non-sense variant (p.Arg792*) in GLI3. Conclusion: The study expands the spectrum of the variants in the GLI3 gene linked to GCPS, and should also facilitate genetic counseling of GCPS patients in the Pakistani population.