Coffin-Siris syndrome is a SWI/SNF complex disorder.

Area of Science:

• Genetics
• Molecular Biology
• Developmental Biology

Background:

• Coffin-Siris syndrome (CSS) is a rare congenital disorder.
• Key features include intellectual disability, growth deficiency, microcephaly, coarse facial features, and nail abnormalities.
• Previous research identified mutations in five SWI/SNF complex genes in CSS patients.

Purpose of the Study:

• To investigate genetic mutations in patients with suspected Coffin-Siris syndrome.
• To further elucidate the role of the SWI/SNF complex in CSS pathogenesis.

Main Methods:

• Whole-exome sequencing and targeted resequencing were performed on 49 new and 3 previously uncharacterized patients.
• High-resolution melting analysis was used for re-examination of select patients.
• Parental samples were analyzed to determine the inheritance pattern of mutations.

Main Results:

• Mutations in SMARCB1, SMARCA4, or ARID1B were identified in 20 patients.
• 17 of these mutations were de novo.
• Mutations in SMARCB1 and SMARCA4 were non-truncating, while ARID1B mutations were truncating.

Conclusions:

• The findings strongly support that Coffin-Siris syndrome is a disorder associated with the SWI/SNF chromatin-remodeling complex.
• Genetic analysis continues to refine the understanding of CSS etiology.
• Specific mutation types in different genes may have distinct implications for CSS.