Unexpected role of <i>SIX1</i> variants in craniosynostosis: expanding the phenotype of <i>SIX1</i>-related disorders.

ABSTRACT:

Background

Pathogenic heterozygous SIX1 variants (predominantly missense) occur in branchio-otic syndrome (BOS), but an association with craniosynostosis has not been reported.

Methods

We investigated probands with craniosynostosis of unknown cause using whole exome/genome (n=628) or RNA (n=386) sequencing, and performed targeted resequencing of SIX1 in 615 additional patients. Expression of SIX1 protein in embryonic cranial sutures was examined in the Six1^nLacZ/+ reporter mouse.

Results

From 1629 unrelated cases with craniosynostosis we identified seven different SIX1 variants (three missense, including two de novo mutations, and four nonsense, one of which was also present in an affected twin). Compared with population d

SUBMITTER: Calpena E 

PROVIDER: S-EPMC8273188 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature