title: Extended spectrum of MBD5 mutations in neurodevelopmental disorders.
abstract: Intellectual disability (ID) is a clinical sign reflecting diverse neurodevelopmental disorders that are genetically and phenotypically heterogeneous. Just recently, partial or complete deletion of methyl-CpG-binding domain 5 (MBD5) gene has been implicated as causative in the phenotype associated with 2q23.1 microdeletion syndrome. In the course of systematic whole-genome screening of individuals with unexplained ID by array-based comparative genomic hybridization, we identified de novo intragenic deletions of MBD5 in three patients leading, as previously documented, to haploinsufficiency of MBD5. In addition, we described a patient with an unreported de novo MBD5 intragenic duplication. Reverse transcriptase-PCR and sequencing analyses showed the presence of numerous aberrant transcripts leading to premature termination codon. To further elucidate the involvement of MBD5 in ID, we sequenced ten coding, five non-coding exons and an evolutionary conserved region in intron 2, in a selected cohort of 78 subjects with a phenotype reminiscent of 2q23.1 microdeletion syndrome. Besides variants most often inherited from an healthy parent, we identified for the first time a de novo nonsense mutation associated with a much more damaging phenotype. Taken together, these results extend the mutation spectrum in MBD5 gene and contribute to refine the associated phenotype of neurodevelopmental disorder.
authors: Laboratoire de Génétique, EA 4368, Université de Lorraine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France.
authors: Céline
authors: C
authors: Bonnet
authors: Asma
authors: A
authors: Ali Khan
authors: Emmanuel
authors: E
authors: Bresso
authors: Charlène
authors: C
authors: Vigouroux
authors: Mylène
authors: M
authors: Béri
authors: Sarah
authors: S
authors: Lejczak
authors: Bénédicte
authors: B
authors: Deemer
authors: Joris
authors: J
authors: Andrieux
authors: Christophe
authors: C
authors: Philippe
authors: Anne
authors: A
authors: Moncla
authors: Irina
authors: I
authors: Giurgea
authors: Marie-Dominique
authors: MD
authors: Devignes
authors: Bruno
authors: B
authors: Leheup
authors: Philippe
authors: P
authors: Jonveaux
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D020131:Genes, Duplicate / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C550332:MBD5 protein, human