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Keywords: Genome sequencing; Malformation; Mendelian disorder; Rare variants; Diagnostics

Authors:
F. Sekiguchi 1; N. Miyake 1; Y. Tsurusaki 1,2; N. Matsumoto 1

Affiliations:
1) Department of Human Genetics, Graduate school of medicine, Yokohama City University, Yokohama, Kanagawa, Japan; 2) Faculty of Nutritional Science, Sagami Women's University, Sagamihara, Kanagawa, Japan


Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of fifth fingers and nails. Pathogenic variants were found in genes encoding BRG1- or HBRM-associated factors (BAF) complex. To date, more than 120 patients with pathogenic variants in 9 BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. We newly recruited 182 CSS-suspected patients. In 182 patients together with previously unresolved 32 patients, we found 77 pathogenic variants in 77 patients. Pathogenic variants in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1 and PHF6 were found in 47, 8, 7, 6, 4, 1 and 1 patients, respectively. In addition, pathogenic CNVs including duplication of SMARCA2 were found in 3 patients. No novel genes with pathogenic variants have been identified. Of note, we first found a partial deletion of SMARCB1 in a CSS patient.