Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort

• DOI: 10.1111/j.1478-3231.2011.02503.x
• Publication Date: 2011-03-14T04:17:16Z
• Authors: Beom H. Lee; Joo H. Kim; Sun Y. Lee; Hye Y. Jin; Kwi-Joo Kim; Jin-Joo Lee; Jung-Young Park; Gu-Hwan Kim; Jin-Ho Choi; Kyung M. Kim; Han-Wook Yoo
• Keywords: Clinical phenotype

Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal this was to identify factors related these diversities.Clinical courses molecular genetic characteristics were analysed 237 unrelated Korean WD families. average follow-up period 8.2 ± 5.8 years.Presenting phenotypes classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX presymptomatic (22.4%) other modifying guidelines by Ferenci colleagues. Age at presentation youngest cirrhosis rarest group. Decompensated highest Favourable outcome Forty-seven (11 novel) ATP7B mutations identified 85% 474 alleles. Multiplex ligation-dependent probe amplification assays analyses ATOX1 COMMD1 genes no additional mutations. Yeast complementation demonstrated functional perturbation seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 p.Leu1083Phe, accounted for 63% more common, age younger N1+N2+NX tended be less common patients with nonsense, frame shifting or splicing than those alone. Patients both transduction (Td) ATP hinge domain showed hepatic manifestations but neurological manifestation.The presenting phenotype strongly affects clinical WD, is mutation type location, providing an evidence genotype-phenotype correlations WD.