Format

Send to

Choose Destination
Eur J Hum Genet. 2014 Feb;22(2):289-92. doi: 10.1038/ejhg.2013.113. Epub 2013 May 15.

Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability.

Author information

1
Departement de Genetique Medicale, Centre de Reference Maladies Rares Anomalies du Developpement et Syndromes Malformatifs Sud-Languedoc Roussillon, Hopital Arnaud de Villeneuve CHRU Montpellier, Faculte de Medecine Universite Montpellier 1, Montpellier, France.
2
Institut fur Humangenetik, Universitatsklinikum Essen, Universitat Duisburg-Essen Hufelandstr, Essen, Germany.
3
Humangenetisches Institut Erlangen, Universitat Erlangen-Nurnberg, Erlangen, Germany.
4
Service de Genetique Chromosomique, Plateforme Puce a ADN, Hopital Arnaud de Villeneuve, CHRU Montpellier,Montpellier, France.
5
1] Service de Genetique Chromosomique, Plateforme Puce a ADN, Hopital Arnaud de Villeneuve, CHRU Montpellier,Montpellier, France [2] Laboratoire de Genetique, Unite Medicale des Maladies Auto-Inflammatoire, Hopital Arnaud de Villeneuve, CHRU Montpellier, Faculte de Medecine, Universite Montpellier, Montpellier, France.
6
Département de génétique médicale, Unité de génétique clinique, CHU de Marseille, Hôpital de la Timone, Marseille, France.
7
Departement de Neuropediatrie, Hopital St Eloi, CHRU Montpellier, Montpellier, France.
8
Departement de Genetique, Hopital Jeanne de Flandre, CHRU Lille, Lille, France.
9
Laboratoire de Genetique, Unite Medicale des Maladies Auto-Inflammatoire, Hopital Arnaud de Villeneuve, CHRU Montpellier, Faculte de Medecine, Universite Montpellier, Montpellier, France.
10
UF de Genetique Moleculaire et de Biochimie, Pole Biologie et Pharmacie, CHU Robert Debre, APHP.

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.

PMID:
23674175
PMCID:
PMC3895633
DOI:
10.1038/ejhg.2013.113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center