Haploinsufficiency of ARID1B, a Member of the SWI/SNF-a Chromatin-remodeling Complex, is a Frequent Cause of Intellectual Disability

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2012 Mar 13

PMID 22405089

Citations 138

Authors

Juliane Hoyer

Arif B Ekici

Sabine Endele

Bernt Popp

Christiane Zweier

Antje Wiesener

Eva Wohlleber

Andreas Dufke

Eva Rossier

Corinna Petsch

Markus Zweier

Ina Gohring

Alexander M Zink

Gudrun Rappold

Evelin Schrock

Dagmar Wieczorek

Olaf Riess

Hartmut Engels

Anita Rauch

Andre Reis

Affiliations

Soon will be listed here.

Abstract

Intellectual disability (ID) is a clinically and genetically heterogeneous common condition that remains etiologically unresolved in the majority of cases. Although several hundred diseased genes have been identified in X-linked, autosomal-recessive, or syndromic types of ID, the establishment of an etiological basis remains a difficult task in unspecific, sporadic cases. Just recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported as relatively common causes of ID in such individuals. On the basis of a patient with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region 6q25, we performed mutational analysis in 887 unselected patients with unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense or frameshift mutations predicted to cause haploinsufficiency. Our findings indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin-remodeling complex, is a common cause of ID, and they add to the growing evidence that chromatin-remodeling defects are an important contributor to neurodevelopmental disorders.

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