The phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish kindreds and a literature review of Alstrom syndrome in Turkey

Basit Öğe Kaydı
dc.contributor.authorOzanturk, Aysegul
dc.contributor.authorMarshall, Jan D.
dc.contributor.authorCollin, Gayle B.
dc.contributor.authorDuzenli, Selma
dc.contributor.authorMarshall, Robert P.
dc.contributor.authorCandan, Sukru
dc.contributor.authorTos, Tulay
dc.date.accessioned2024-04-24T16:24:03Z
dc.date.available2024-04-24T16:24:03Z
dc.date.issued2015
dc.departmentDicle Üniversitesien_US
dc.description.abstractAlstrom syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alstrom Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alstrom Syndrome and contribute to genotype-phenotype correlation studies.en_US
dc.description.sponsorshipNIH [HD036878]; DPT [1206400603]; TUBITAK [111S217]; Turkeyen_US
dc.description.sponsorshipWe are grateful to Alstrom Syndrome International and Nevin Bengur, Alstrom Syndrome-Canada, Alstrom Sendromu Dernegi Turkey. We are grateful to A Dufke, A Kiraz, F Silan, H Onal, JR Lupski, N Narin, O Cogulu, S Gunis-Bilgili, S Tasdemir, T Ucar, Y Seckin, and many physicians who referred their patients for this study. This study was supported, in part, by NIH HD036878 (JKN, JDM, GBC), DPT 1206400603 and TUBITAK, 111S217, Turkey (AO and RKO).en_US
dc.identifier.doi10.1038/jhg.2014.85
dc.identifier.endpage9en_US
dc.identifier.issn1434-5161
dc.identifier.issn1435-232X
dc.identifier.issue1en_US
dc.identifier.pmid25296579
dc.identifier.scopus2-s2.0-84922283783
dc.identifier.scopusqualityQ1
dc.identifier.startpage1en_US
dc.identifier.urihttps://doi.org/10.1038/jhg.2014.85
dc.identifier.urihttps://hdl.handle.net/11468/16438
dc.identifier.volume60en_US
dc.identifier.wosWOS:000348684000001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofJournal of Human Genetics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keyword]en_US
dc.titleThe phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish kindreds and a literature review of Alstrom syndrome in Turkeyen_US
dc.titleThe phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish kindreds and a literature review of Alstrom syndrome in Turkey
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu