Refining the regulatory region upstream of SOX9 associated with 46,XX testicular disorders of Sex Development (DSD).
Am J Med Genet A
; 167A(8): 1851-8, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25900885
ABSTRACT
Disorders of Sex Development (DSD) are a heterogeneous group of disorders affecting gonad and/or genito-urinary tract development and usually the endocrine-reproductive system. A genetic diagnosis is made in only around 20% of these cases. The genetic causes of 46,XX-SRY negative testicular DSD as well as ovotesticular DSD are poorly defined. Duplications involving a region located â¼600 kb upstream of SOX9, a key gene in testis development, were reported in several cases of 46,XX DSD. Recent studies have narrowed this region down to a 78 kb interval that is duplicated or deleted respectively in 46,XX or 46,XY DSD. We identified three phenotypically normal patients presenting with azoospermia and 46,XX testicular DSD. Two brothers carried a 83.8 kb duplication located â¼600 kb upstream of SOX9 that overlapped with the previously reported rearrangements. This duplication refines the minimal region associated with 46,XX-SRY negative DSD to a 40.7-41.9 kb element located â¼600 kb upstream of SOX9. Predicted enhancer elements and evolutionary-conserved binding sites for proteins known to be involved in testis determination are located within this region.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos do Desenvolvimento Sexual
/
Sequências Reguladoras de Ácido Nucleico
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Aberrações Cromossômicas
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Fatores de Transcrição SOX9
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article