Two nonsense GLI3 variants are associated with polydactyly and syndactyly in two families by affecting the sonic hedgehog signaling pathway.

ABSTRACT:

Background

Polydactyly and syndactyly are congenital limb deformities, segregating in an autosomal-dominant fashion. The variants in the GLI3 gene are closely related to congenital limb malformations. However, the causes underlying polydactyly and syndactyly are not well understood.

Methods

We conducted a whole-exome sequencing on two four-generation Chinese families with polydactyly and syndactyly. Then c.2374C>T and c.1728C>A mutant plasmids were transfected to HEK293T cells and mice limb bud cells to explore the functional consequences of these variants. Western blot and real-time quantitative PCR were used to analyze the expression of GLI3 and Shh.

Results

In these two families, the known GLI3 variant (NM_000168.6:c.2374C>T) and the novel GLI3 variant (NM_000168.6

SUBMITTER: Shen X 

PROVIDER: S-EPMC9000928 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature