Genotype-Phenotype Correlations in a Mountain Population Community with High Prevalence of Wilson’s

Wilson’s disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson’s disease ever reported of 1:1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (1861 years) showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson’s disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson’s disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities. Citation: Cocoş R, Şendroiu A, Schipor S, Bohı̂lţea LC, Şendroiu I, et al. (2014) Genotype-Phenotype Correlations in a Mountain Population Community with High Editor: Bart Dermaut, Pasteur Institute of Lille, France Received March 8, 2014; Accepted April 29, 2014; Published June 4, 2014 Copyright: 2014 Cocoş et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. Sequence data are included within the Supporting Information files. Funding: This work was financially supported by two grants of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project numbers 2005CNCSIS-27677 and PN-II-ID-PCCE 2011-2-0013. www.cncs-nrc.ro and http://uefiscdi.gov.ro/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: florina_raicu@yahoo.com