Genetic study of SOX9 in a case of campomelic dysplasia.
Am J Med Genet
; 98(2): 176-81, 2001 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-11223854
Campomelic dysplasia (CD) is a sporadic autosomal dominant syndrome that results in skeletal malformation and developmental abnormalities. Death usually occurs neonatally as a result of respiratory insufficiencies, but life expectancy varies depending on the severity of the phenotype. XY sex reversal is common in CD, and a range of genital defects is observed in males and females. CD is due to mutations in SOX9, a member of the SOX (SRY-related HMG box) gene family. SOX9 is a transcription factor involved in chondrogenesis and sex determination. We present a CD patient with a normal 46,XX karyotype and female phenotype. Single-stranded conformation polymorphism analysis of DNA from this CD patient demonstrated a single-stranded conformation polymorphism shift in the C-terminal region of SOX9. DNA sequencing showed a frameshift mutation resulting from the insertion of a single guanine residue in nucleotide region 1,453-1,456. This insertion mutation creates a mutant SOX9 open reading frame that is 201 nucleotides longer than the normal gene. It has been shown that the C-terminal region of SOX9 is responsible for the transactivating ability of the protein. The frameshift identified here affects approximately half of the protein region needed for full transactivating function. We hypothesize that residual SOX9 function may explain why this patient survived infancy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteocondrodisplasias
/
Factores de Transcripción
/
Análisis Mutacional de ADN
/
Proteínas del Grupo de Alta Movilidad
/
Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Am J Med Genet
Año:
2001
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos