Identification of disrupted AUTS2 and EPHA6 genes by array painting in a patient carrying a de novo balanced translocation t(3;7) with intellectual disability and neurodevelopment disorder.
Intellectual disability (ID) is a frequent feature but is highly clinically and genetically heterogeneous. The establishment of the precise diagnosis in patients with ID is challenging due to this heterogeneity but crucial for genetic counseling and appropriate care for the patients. Among the etiologies of patients with ID, apparently balanced de novo rearrangements represent 0.6%. Several mechanisms explain the ID in patients with apparently balanced de novo rearrangement. Among them, disruption of a disease gene at the breakpoint, is frequently evoked. In this context, technologies recently developed are used to characterize precisely such chromosomal rearrangements. Here, we report the case of a boy with ID, facial features and autistic behavior who is carrying a de novo balanced reciprocal translocation t(3;7)(q11.2;q11.22)dn. Using microarray analysis, array painting (AP) technology combined with molecular study, we have identified the interruption of the autism susceptibility candidate 2 gene (AUTS2) and EPH receptor A6 gene (EPHA6). We consider that the disruption of AUTS2 explains the phenotype of the patient; the exact role of EPHA6 in human pathology is not well defined. Based on the observation of recurrent germinal and somatic translocations involving AUTS2 and the molecular environment content, we put forward the hypothesis that the likely chromosomal mechanism responsible for the translocation could be due either to replicative stress or to recombination-based mechanisms.
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Anouck
A
Schneider
Département de Génétique Médicale, CHRU de Montpellier, France.
Jacques
J
Puechberty
Cytometry Core Facility, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Bee Ling
BL
Ng
Département de Génétique Médicale, CHRU de Montpellier, France.
Christine
C
Coubes
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Vincent
V
Gatinois
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Magali
M
Tournaire
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Manon
M
Girard
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Bruno
B
Dumont
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Pauline
P
Bouret
CRA, Département de Psychiatrie de l'Enfant et de l'Adolescent, Centre de Ressources Autisme, CHRU de Montpellier, France.
Julia
J
Magnetto
CRA, Département de Psychiatrie de l'Enfant et de l'Adolescent, Centre de Ressources Autisme, CHRU de Montpellier, France.
Amaria
A
Baghdadli
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.
Franck
F
Pellestor
Laboratoire de Génétique Chromosomique, Plateforme de puces à ADN, CHRU de Montpellier, France.|Département de Génétique Médicale, CHRU de Montpellier, France.
David
D
Geneviève
D001483:Base Sequence; D002648:Child; D020223:Chromosome Painting / Q000379:methods; D002893:Chromosomes, Human, Pair 3; D002897:Chromosomes, Human, Pair 7; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D065886:Neurodevelopmental Disorders / Q000235:genetics*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D036124:Receptor, EphA6 / Q000235:genetics*; D014157:Transcription Factors; D014178:Translocation, Genetic
C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D014157:Transcription Factors; D036124:Receptor, EphA6
AUTS2; array painting; balanced translocation; intellectual disability