title: Intragenic duplication--a novel causative mechanism for SATB2-associated syndrome.
abstract: Previous studies have shown that genetic aberrations involving the special AT-rich sequence-binding protein 2 (SATB2) gene result in a variable phenotype of syndromic intellectual disability. Although only a small number of patients have been described, there is already considerable variation in regard to the underlying molecular mechanism spanning from structural variation to point mutations. We here describe a male patient with intellectual disability, speech and language impairment, cleft palate, malformed teeth, and oligodontia. Array CGH analysis identified a small intragenic duplication in the SATB2 gene that included three coding exons. The result was confirmed by multiplex ligation-dependent probe amplification and low coverage whole genome mate pair sequencing. WGS breakpoint analysis directly confirmed the duplication as intragenic. This is the first reported patient with an intragenic duplication in SATB2 in combination with a phenotype that is highly similar to previously described patients with small deletions or point mutations of the same gene. Our findings expand the spectra of SATB2 mutations and confirm the presence of a distinct SATB2-phenotype with severe ID and speech impairment, cleft palate and/or high arched palate, and abnormalities of the teeth. For patients that present with this clinical picture, a high-resolution exon targeted array CGH and/or WGS, in addition to sequencing of SATB2, should be considered.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Agne
authors.initials: A
authors.lastname: Liedén
authors.forename: Malin
authors.initials: M
authors.lastname: Kvarnung
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilssson
authors.forename: Ellika
authors.initials: E
authors.lastname: Sahlin
authors.forename: Elisabeth Syk
authors.initials: ES
authors.lastname: Lundberg
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D017931:DNA Primers / Q000235:genetics; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: 2q33.1; SATB2; array comparative genomic hybridization; cleft palate; intellectual disability; mate pair sequencing; speech impairment; teeth abnormality