1. Characterization of a Putative Founder Mutation that Accounts for the High Incidence of Cystinosis in Brittany
- Author
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Geneviève Jean, Béatrice Cordier, Vasiliki Kalatzis, Pierre Cochat, Corinne Antignac, Stephanie Cherqui, and Michel Broyer
- Subjects
Adult ,Adolescent ,RNA Splicing ,Cystinosis ,Molecular Sequence Data ,Biology ,Exon ,medicine ,Humans ,Allele ,Child ,Genetics ,Base Sequence ,Incidence ,Incidence (epidemiology) ,Intron ,General Medicine ,medicine.disease ,Phenotype ,Founder Effect ,Cystinosin ,Nephrology ,Mutation ,Mutation (genetic algorithm) ,RNA ,France ,Gene Deletion - Abstract
Cystinosis is an autosomal recessive disorder, char- acterized by an accumulation of intralysosomal cystine, with an incidence of 1 in 100,000 to 200,000 live births. A higher incidence of cystinosis, 1 in 26,000 live births, has been reported in the western French province of Brittany. PCR amplification and sequencing has identified a 27-bp deletion starting 3 bp before the end of exon 8 and continuing into intron 8, 898-90024del27, which has only been detected in families from this region. Reverse transcription-PCR amplifi- cation of RNA from an affected individual has shown that this mutation is indeed a splice-site mutation and results in the production of aberrant transcripts. These transcripts are pre- dicted to either severely truncate cystinosin or alter its topol- ogy, thus accounting for the severe phenotype of these indi- viduals. The mutation 898-90024del27 has been identified in 7 of 18 alleles studied. This mutation is likely to be a founder mutation and would account for the higher incidence of cysti- nosis in Brittany. 1
- Published
- 2001
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