Abstract
Coffin-Siris syndrome1 (CSS1; Online Mendelian Inheritance in Man no. 135900) is a multiple malformation syndrome characterized by intellectual and/or developmental delay, and hypoplastic or absent fifth fingernails and/or toenails. AT-rich interaction domain-containing protein 1B (ARID1B) is the most frequently mutated gene in CSS1 and the majority of reported cases have been sporadic. Using whole-exome sequencing, the present study identified two siblings with CSS1 with a novel heterozygous co-segregating pathogenic variant in the ARID1B gene (c.3468_3471del). Additionally, the current study confirmed a 4% somatic ARID1B mosaicism in the patient's mother. The results expanded the spectrum of known ARID1B pathogenic variants. To the best of our knowledge, the present study is the first to provide experimental evidence that an ARID1B pathogenic variant can be inherited from a clinically healthy somatogonadal mosaic mother.