Intragenic duplication--a novel causative mechanism for SATB2-associated syndrome.
Am J Med Genet A
; 164A(12): 3083-7, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25251319
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Fatores de Transcrição
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Anormalidades Múltiplas
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Duplicação Gênica
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Proteínas de Ligação à Região de Interação com a Matriz
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Deficiência Intelectual
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article