A-2-->G transition at the 3' acceptor splice site of IVS17 characterizes the COL2A1 gene mutation in the original Stickler syndrome kindred.
Am J Med Genet
; 63(3): 461-7, 1996 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-8737653
ABSTRACT
Hereditary progressive arthro-ophthalmopathy, or "Stickler syndrome," is an autosomal dominant osteochondrodysplasia characterized by a variety of ocular and skeletal anomalies which frequently lead to retinal detachment and precocious osteoarthritis. A variety of mutations in the COL2A1 gene have been identified in "Stickler" families; in most cases studied thus far, the consequence of mutation is the premature generation of a stop codon. We report here the characterization of a COL2A1 gene mutation in the original kindred described by Stickler et al. [1965]. Conformational sensitive gel electrophoresis (CSGE) [Ganguly et al., 1993] was used to screen for mutations in the entire COL2A1 gene in an affected member from the kindred. A prominent heteroduplex species was noted in the polymerase chain reaction (PCR) product from a region of the gene including exons 17 to 20. Direct sequencing of PCR-amplified genomic DNA resulted in the identification of a base substitution at the A-2 position of the 3' splice acceptor site of IVS17. Sequencing of DNA from affected and unaffected family members confirmed that the mutation segregated with the disease phenotype. Reverse transcriptase-PCR analysis of poly A+ RNA demonstrated that the mutant allele utilized a cryptic splice site in exon 18 of the gene, eliminating 16 bp at the start of exon 18. This frameshift eventually results in a premature termination codon. These findings are the first report of a splice site mutation in classical Stickler syndrome and they provide a satisfying historical context in which to view COL2A1 mutations in this dysplasia.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Descolamento Retiniano
/
Splicing de RNA
/
Colágeno
/
Oftalmopatias
/
Artropatias
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Aged
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
/
Newborn
Idioma:
En
Revista:
Am J Med Genet
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos