A rare Coffin-Siris syndrome induced by SOX11: a de novo nonsense variant of short stature

Abstract

Background Coffin-Siris syndrome is a clinically elusive and rare genetic disease characterized by a wide range of clinical manifestations. This study deeply analyzed and identified the clinical phenotype and genetic variant location in a pediatric patient with Coffin-Siris syndrome, aiming to enhance the understanding of this syndrome and assist in its screening and diagnosis. Methods A combination of advanced diagnostic tools, including high-throughput whole-exome sequencing (WES) and first-generation sequencing technologies, was employed to ascertain the etiology of the disease in the child. Results The clinical phenotype was characterized by stunted growth, reduced stature, spina bifida, enuresis, and a ventricular septal defect. WES revealed a de novo variant in the SOX11 gene locus (c.700G > T), identified as pathogenic. It is noteworthy that this variant has not been previously reported. Conclusions The combination of clinical presentation and genetic testing results supports that the patient suffers from Coffin-Siris syndrome due to a genetic variant in the SOX11 gene. This de novo variant expands our understanding of human gene variation, which is conducive to genetic counseling and screening for early diagnosis of Coffin-Siris syndrome. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-024-02036-w.