Partial COL1A2 gene duplication produces features of osteogenesis imperfecta and Ehlers-Danlos syndrome type VII.
Hum Genet
; 106(1): 19-28, 2000 Jan.
Article
en En
| MEDLINE
| ID: mdl-10982177
Type I collagen is the most abundant structural protein in the mammalian body. It exists as a heterotrimer of two subunits in the form [alpha1(I)]2alpha2(I). Pathogenic mutations in COL1A1 and COL1A2, the genes that encode the two subunits, cause a range of phenotypes including mild to lethal forms of osteogenesis imperfecta and a restricted set of Ehlers-Danlos syndrome phenotypes. Lethal mutations usually result from missense mutations that disrupt the normal triple helical structure of the molecule. Multi-exon duplication or deletion in type I collagen genes has rarely been observed and has generally resulted in a lethal or severe phenotype. We report a partial duplication in the COLIA2 gene that causes a relatively mild phenotype, despite the addition of 477 amino acids to the triple helical domain of the proalpha2(I) chain. The abnormal molecule is synthesized and secreted by cultured dermal fibroblasts in a normal fashion. Electron microscopy of dermal tissue reveals small but otherwise near normal collagen fibrils. The gene duplication occurred by mitotic sister chromatid exchange in the mother who is mosaic for the duplication allele. Examination of the abnormal sequence suggests a means by which the duplicated molecule could be processed and properly incorporated into mature collagen fibrils.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis Imperfecta
/
Colágeno
/
Duplicación de Gen
/
Síndrome de Ehlers-Danlos
Límite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Hum Genet
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania