Mutation profiling in South African patients with Cornelia de Lange syndrome phenotype

Abstract Background Cornelia de Lange Syndrome (CdLS) presents with a variable multi‐systemic phenotype and pathogenic variants have been identified in five main genes. This condition has been understudied in African populations with little phenotypic and molecular information available. Methods and Results We present a cohort of 14 patients with clinical features suggestive of CdLS. Clinical phenotyping was carried out and cases were classified according to the international consensus criteria. According to this criteria, nine patients had classical CdLS, one had non‐classical CdLS and four presented with a phenotype that suggested molecular testing for CdLS. Each patient underwent mutation profiling using a targeted next generation sequencing panel of 18 genes comprising known and suspected CdLS causal genes. Of the 14 patients tested, pathogenic and likely pathogenic variants were identified in nine: eight variants in the NIPBL gene and one in the STAG1 gene. Conclusions We present the first molecular data for a cohort of South African patients with CdLS. Eight of the nine variants identified were in the NIPBL gene, the most commonly involved gene in cases of CdLS. This is also the first report of a patient of African ancestry presenting with STAG1 ‐related CdLS.