Duncan NRI Faculty and Staff Publications

Language

English

Publication Date

9-1-2022

Journal

American Journal of Medical Genetics Part A

DOI

10.1002/ajmg.a.62889

PMID

35796094

PMCID

PMC9378577

PubMedCentral® Posted Date

9-1-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and a review of the literature, provide evidence that deleterious variants in ARID1B, ARID1A, SMARCB1, SMARCA4, SMARCE1, ARID2, DPF2, and SMARCC2, which are associated with CSS types 1-8, respectively, are associated with the development of CDH. This suggests that additional genetic testing to identify a separate cause of CDH in an individual with CSS may be unwarranted, and that comprehensive genetic testing for individuals with non-isolated CDH should include an evaluation of CSS-related genes. These data also suggest that the mSWI/SNF (BAF) complex may play an important role in diaphragm development.

Keywords

Abnormalities, Multiple, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Face, Hand Deformities, Congenital, Hernias, Diaphragmatic, Congenital, Humans, Intellectual Disability, Micrognathism, Neck, Nuclear Proteins, Transcription Factors, congenital diaphragmatic hernia, CDH, Coffin-Siris syndrome, exome sequencing

Published Open-Access

yes

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