title: High prevalence of W1282x mutation in cystic fibrosis patients from Karachay-Cherkessia.
abstract: Cystic fibrosis (CF; OMIM #219700) is a common autosomal recessive disease. The spectrum and frequency of CFTR mutations vary significantly in different populations and ethnic groups. A genetic epidemiological study was conducted in the indigenous ethnic group of people known as the Karachais. They live in the Republic of Karachay-Cherkessia, which lies in the northwest of Russia's North Caucasus region. Karachai's are Turkic-speaking and consist of 194 thousand people (approximately 40% of the population of the Republic). Molecular genetic analysis was performed in 10 unrelated Karachai families with CF patients from three districts in the Republic. A high frequency of W1282X mutation was found (18 of 20 mutant alleles): eight patients were homozygous for the W1282X mutation, and two were compound heterozygous (the second alleles were R1066C and R709X). Analysis for 13 common CF mutations in the sample of 142 healthy Karachais identified two 1677delTA and two W1282X mutation carriers. Thus, the most common CFTR mutation, F508del, was not detected among the CF patients or in healthy Karachais. The most frequent mutation among Karachai patients is W1282X (90%). Its frequency in healthy Karachais is approximately 0.007. Haplotype analysis using the CFTR intragene DNA markers IVS1CA, IVS6aGATT, IVS8CA and IVS17bCA showed that the origins of the W1282X mutation in Karachay-Cherkessia and the Eastern European part of Russia are different.
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: npetrova63@mail.ru.
authors.forename: N V
authors.initials: NV
authors.lastname: Petrova
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: kashirskayanj@mail.ru.
authors.forename: N Yu
authors.initials: NY
authors.lastname: Kashirskaya
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation.
authors.forename: T A
authors.initials: TA
authors.lastname: Vasilyeva
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: timkovskaja@rambler.ru.
authors.forename: E E
authors.initials: EE
authors.lastname: Timkovskaya
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: voronkova111@yandex.ru.
authors.forename: A Yu
authors.initials: AY
authors.lastname: Voronkova
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: shabalova@list.ru.
authors.forename: L A
authors.initials: LA
authors.lastname: Shabalova
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: elenafpk@mail.ru.
authors.forename: E I
authors.initials: EI
authors.lastname: Kondratyeva
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: tovika@yandex.ru.
authors.forename: V D
authors.initials: VD
authors.lastname: Sherman
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: lgnovoselova@gmail.com.
authors.forename: O G
authors.initials: OG
authors.lastname: Novoselova
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation. Electronic address: nikolay.i.kapranov@gmail.com.
authors.forename: N I
authors.initials: NI
authors.lastname: Kapranov
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation; Pirogov Russian National Research Medical University, Ostrovityanova St., 1, Moscow 117997, Russian Federation; Moscow State University of Medicine and Dentistry, Delegatskaya St., 20 bld. 1, Moscow 127473, Russian Federation. Electronic address: renazinchenko@mail.ru.
authors.forename: R A
authors.initials: RA
authors.lastname: Zinchenko
authors.affiliation: Federal State Budgetary Institution, Research Centre for Medical Genetics, Moskvorechje St., 1, Moscow 115478, Russian Federation; Russian Medical Academy of Postgraduate Education, Barrikadnaya St., 2/1, Moscow 125993, Russian Federation. Electronic address: ekginter@mail.ru.
authors.forename: E K
authors.initials: EK
authors.lastname: Ginter
authors.affiliation: Municipal Budgetary Health Care Institution, Habezskaya Central District Hospital, Karachay-Cherkessia Republic, Habez, 6, Bolnichnaya Str., Russian Federation. Electronic address: makaov@yandex.ru.
authors.forename: A Kh-M
authors.initials: AKh
authors.lastname: Makaov
authors.affiliation: Department of Genetics, The Hebrew University of Jerusalem, 91904, Israel. Electronic address: batshevak@savion.huji.ac.il.
authors.forename: B
authors.initials: B
authors.lastname: Kerem
mesh_terms: D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D059645:Mutation Rate; D044382:Population Groups / Q000235:genetics / Q000706:statistics & numerical data; D015995:Prevalence; D012426:Russia / Q000453:epidemiology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Cystic fibrosis; Frequency and spectrum of CFTR mutations; Karachais; W1282X