Expanding the Phenotype of IQSEC2 Mutations: Truncating Mutations in Severe Intellectual Disability

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2013 May 16

PMID 23674175

Citations 22

Authors

Frederic Tran Mau-Them

Marjolaine Willems

Beate Albrecht

Elodie Sanchez

Jacques Puechberty

Sabine Endele

Anouck Schneider

Nathalie Ruiz Pallares

Chantal Missirian

Francois Rivier

Manon Girard

Muriel Holder

Sylvie Manouvrier

Isabelle Touitou

Genevieve Lefort

Pierre Sarda

Anne Moncla

Severine Drunat

Dagmar Wieczorek

David Genevieve

Affiliations

Soon will be listed here.

Abstract

Intellectual disability (ID) is frequent in the general population, with 1 in 50 individuals directly affected worldwide. The multiple etiologies include X-linked ID (XLID). Among syndromic XLID, few syndromes present severe ID associated with postnatal microcephaly and midline stereotypic hand movements. We report on three male patients with ID, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures (2/3), and non-inherited and postnatal onset microcephaly (2/3). Using array CGH and exome sequencing we characterised two truncating mutations in IQSEC2, namely two de novo intragenic duplication mapped to the Xp11.22 region and a nonsense mutation in exon 7. We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C.

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