title: Genetic basis of cystinosis in Turkish patients: a single-center experience.
abstract: We report the molecular findings for the CTNS gene in 12 Turkish cystinosis patients aged 7-29 years. All presented initially with severe failure to thrive, polyuria, and polydipsia. Cystinosis was diagnosed at age 1 month to 9 years. Seven patients reached end-stage renal failure at ages ranging from 6.5 to 15 years. Whereas three of the remaining five have renal Fanconi syndrome with proteinuria, two have had kidney failure of varying degrees. Molecular analyses involved an initial multiplex polymerase chain reaction (PCR) to determine the presence or absence of the 57-kb northern European founder deletion in CTNS, followed by sequencing of the ten coding exons of CTNS. Comprehensive mutation analysis verified that none of the 12 patients carried the common 57-kb deletion. We identified four previously reported nucleotide variations associated with cystinosis and five new variants: a 10-kb deletion, three missense variants, and a nucleotide substitution in a potential branch point site of intron 4. This study is the first molecular analysis of Turkish cystinosis patients and provides guidance for the molecular diagnosis of cystinosis in this population.
authors.affiliation: Dept of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey. rezantopaloglu@hacettepe.edu.tr
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.forename: Thierry
authors.initials: T
authors.lastname: Vilboux
authors.forename: Turgay
authors.initials: T
authors.lastname: Coskun
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Brad
authors.initials: B
authors.lastname: Tinloy
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.forename: Aysin
authors.initials: A
authors.lastname: Bakkaloglu
authors.forename: Nesrin
authors.initials: N
authors.lastname: Besbas
authors.forename: Lambert
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D000328:Adult; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D003554:Cystinosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons; D005183:Failure to Thrive / Q000235:genetics; D005198:Fanconi Syndrome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D017354:Point Mutation; D059606:Polydipsia / Q000235:genetics; D016133:Polymerase Chain Reaction; D011141:Polyuria / Q000235:genetics; D011507:Proteinuria / Q000235:genetics; D051437:Renal Insufficiency / Q000235:genetics; D017384:Sequence Deletion; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C111445:CTNS protein, human