De Novo SMARCC2 Variant in a Chinese Woman with Coffin-Siris Syndrome 8: a Case Report with Mild Intellectual Disability and Endocrinopathy.

Abstract

Coffin-Siris syndrome (CSS) is a neurodevelopmental disorder characterized by cognitive disability, coarse facial features, hypertrichosis, and somatic dysmorphic features. It is caused by mutations in the BAF-complex or SOX gene. Here, a Chinese woman presenting with neurodevelopmental delay, mild intellectual disability, speech delay, dysmorphic features, obesity, scoliosis, hypotonia, seizures, skin problems, hypokalemia, and endocrine dysfunction is described. Whole exome sequencing (WES) identified a heterozygous missense variant, c.2074G > C (p. Ala692Pro), in the SMARCC2 gene of the proband. Affecting chromatin structure, SMARCC2 plays an essential role in modulating cortical neurogenesis, and controlling cortical size and thickness. Moreover, it is associated with tumor suppression, and SMARCC2 mutations have been observed with high frequency in human cancers. While this is the second report of SMARCC2 mutations in patients with detailed phenotypes, this is the first describing the observation of electrolyte disturbances and endocrinopathy. These findings expanded the genetic and clinical spectrum of SMARCC2-related Coffin-Siris syndrome.