title: Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany.
abstract: Cystinosis is an autosomal recessive disorder, characterized 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, 898-900+24del27, which has only been detected in families from this region. Reverse transcription-PCR amplification 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 predicted to either severely truncate cystinosin or alter its topology, thus accounting for the severe phenotype of these individuals. The mutation 898-900+24del27 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 cystinosis in Brittany.(1)
authors.affiliation: Inserm U423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kalatzis
authors.affiliation: Inserm U423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cherqui
authors.affiliation: Inserm U423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Jean
authors.affiliation: Département de Pédiatrie, Hôpital Edouard Herriot et Université Claude Bernard, Lyon, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Cordier
authors.affiliation: Département de Pédiatrie, Hôpital Edouard Herriot et Université Claude Bernard, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.affiliation: Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Broyer
authors.affiliation: Inserm U423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D002648:Child; D003554:Cystinosis / Q000453:epidemiology* / Q000235:genetics*; D018703:Founder Effect; D005602:France / Q000453:epidemiology; D017353:Gene Deletion; D006801:Humans; D015994:Incidence; D008969:Molecular Sequence Data; D009154:Mutation; D012313:RNA / Q000235:genetics; D012326:RNA Splicing
chemical_list: D012313:RNA