Exome sequencing identifies a de novo mutation in HDAC8 associated with Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. The clinical features of CdLS include growth retardation, intellectual disability, limb defects, typical facial dysmorphism and other systemic involvement. Here, we present the clinical and genetic characterization of a sporadic CdLS trio. The proband is a 7-year-old girl with typical CdLS, and both parents are apparently healthy. Whole-exome sequencing of the patient and of both her unaffected parents revealed a previously unobserved de novo mutation in exon 6 of the HDAC8 gene (chrX: 71684483, c.586 A>T; p.M196K). Thus, we have further founded that the p.M196K mutation in HDAC8 is a relevant causal mutation for CdLS.