title: Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability.
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.
authors.affiliation: 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.
authors.forename: Frederic
authors.initials: F
authors.lastname: Tran Mau-Them
authors.affiliation: 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.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Willems
authors.affiliation: Institut fur Humangenetik, Universitatsklinikum Essen, Universitat Duisburg-Essen Hufelandstr, Essen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Albrecht
authors.affiliation: 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.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: 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.
authors.forename: Jacques
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Humangenetisches Institut Erlangen, Universitat Erlangen-Nurnberg, Erlangen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Endele
authors.affiliation: Service de Genetique Chromosomique, Plateforme Puce a ADN, Hopital Arnaud de Villeneuve, CHRU Montpellier,Montpellier, France.
authors.forename: Anouck
authors.initials: A
authors.lastname: Schneider
authors.affiliation: 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.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ruiz Pallares
authors.affiliation: Département de génétique médicale, Unité de génétique clinique, CHU de Marseille, Hôpital de la Timone, Marseille, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Missirian
authors.affiliation: Departement de Neuropediatrie, Hopital St Eloi, CHRU Montpellier, Montpellier, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Rivier
authors.affiliation: Service de Genetique Chromosomique, Plateforme Puce a ADN, Hopital Arnaud de Villeneuve, CHRU Montpellier,Montpellier, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Girard
authors.affiliation: Departement de Genetique, Hopital Jeanne de Flandre, CHRU Lille, Lille, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder
authors.affiliation: Departement de Genetique, Hopital Jeanne de Flandre, CHRU Lille, Lille, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier
authors.affiliation: Laboratoire de Genetique, Unite Medicale des Maladies Auto-Inflammatoire, Hopital Arnaud de Villeneuve, CHRU Montpellier, Faculte de Medecine, Universite Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
authors.affiliation: Service de Genetique Chromosomique, Plateforme Puce a ADN, Hopital Arnaud de Villeneuve, CHRU Montpellier,Montpellier, France.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Lefort
authors.affiliation: 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.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.affiliation: Departement de Neuropediatrie, Hopital St Eloi, CHRU Montpellier, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.affiliation: UF de Genetique Moleculaire et de Biochimie, Pole Biologie et Pharmacie, CHU Robert Debre, APHP.
authors.forename: Severine
authors.initials: S
authors.lastname: Drunat
authors.affiliation: Institut fur Humangenetik, Universitatsklinikum Essen, Universitat Duisburg-Essen Hufelandstr, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Genevieve
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D002675:Child, Preschool; D018389:Codon, Nonsense; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D010641:Phenotype
chemical_list: D018389:Codon, Nonsense; D020662:Guanine Nucleotide Exchange Factors; C550083:IQSEC2 protein, human