title: Disruption of the ARID1B and ADAMTS6 loci due to a t(5;6)(q12.3;q25.3) in a patient with developmental delay.
abstract: Here, we report on a male patient with developmental delay, speech impairment, mild dysmorphic features, and borderline intellectual disability, bearing a de novo balanced t(5;6)(q11;q25.3). By combining FISH and long distance inverse PCR, we identified two genes, ADAMTS6 and ARID1B, which were disrupted at the translocation breakpoints. Due to the opposing transcriptional directions of the two genes, no fusion transcripts could be formed. ADAMTS6 on chromosome 5 encodes a zinc metalloprotease. To date, there has been no information about the substrates and the exact role of this enzyme protein. ARID1B on chromosome 6 is involved in chromatin remodeling and transcriptional activation and is known to play a role in neural development. To our knowledge, this is the fourth translocation involving ARID1B reported in association with intellectual disability. ARID1B haploinsufficiency has already been described in patients with intellectual disabilities with or without corpus callosum abnormalities, Coffin-Siris syndrome and autism (OMIM 614562 and OMIM 614556). A review of patients with ARID1B mutations reveals their broad phenotypic variability. The phenotype of the present patient is of the mildest described to date and further underscores this observation. We conclude that the most prominent and consistent clinical findings in patients with ARID1B haploinsufficiency are developmental delay, speech impairment and intellectual disability and propose that patients with unresolved genetic background and these clinical findings should be considered for ARID1B mutation screening.
authors.affiliation: Laboratory for Molecular Biology and Tumor Cytogenetics, Department of Internal Medicine I, Hospital Barmherzige Schwestern Linz, Upper Austria, Austria.
authors.forename: Theodora
authors.initials: T
authors.lastname: Malli
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Duba
authors.forename: Martin
authors.initials: M
authors.lastname: Erdel
authors.forename: Renate
authors.initials: R
authors.lastname: Marschon
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kranewitter
authors.forename: Sabine
authors.initials: S
authors.lastname: Deutschbauer
authors.forename: Johanna
authors.initials: J
authors.lastname: Kralik
authors.forename: Evita
authors.initials: E
authors.lastname: Diel
authors.forename: Barbara
authors.initials: B
authors.lastname: Güenther
authors.forename: Doris
authors.initials: D
authors.lastname: Mueller
authors.forename: Gerald
authors.initials: G
authors.lastname: Webersinke
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000015:Abnormalities, Multiple / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C497837:ARID1B protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C121533:Adamts6 protein, human
keywords: ADAMTS6; ARID1B; developmental delay; intellectual disability; speech impairment