Yahata Shinsuke, Yung Seitetsu, Mandai Mari, Nagahara Takakazu, Kuzume Daisaku, Sakaeda Hiroshi, Wakusawa Shinya, Kato Ayako, Tatsumi Yasuaki, Kato Koichi, Hayashi Hisao, Isaji Ryohei, Sasaki Yoji, Yano Motoyoshi, Hayashi Kazuhiko, Ishigami Masatoshi, Goto Hidemi
Department of Gastroenterology, Hyogo Prefectural Kakogawa Medical Center, Kakogawa, Hyogo, Japan.
Department of Gastroenterology and Hepatology, Tottori Prefectural Kousei Hospital, Kurayoshi, Tottori, Japan.
J Clin Transl Hepatol. 2017 Mar 28;5(1):27-30. doi: 10.14218/JCTH.2016.00064. Epub 2017 Feb 22.
Cloning of ATP7B provided evidence that Wilson's disease is a hepatic copper toxicosis with a variety of extrahepatic complications. Affected siblings with the same genetic background and exposure to similar environmental factors may be a good model for the study of genotype-phenotype correlation. Twenty-three affected siblings in 11 families were selected from a database. The first phenotypes were determined according to the international proposal. The final types of chronic organ damage were re-evaluated for life-long management. Phenotypes were identical in 5 of the families and different in 6 of the families. The acute hepatic phenotype was found in 3 younger siblings and 1 older sibling. All survived an acute episode of hemolysis with underlying chronic liver disease. One also presented complication with neurological disease. The neurological phenotype with neuropsychiatric symptoms and hepatic disease was found in 2 aged siblings of 1 family, in an older sibling in 3 families and in the oldest sibling in 1 family. Phenotypes in siblings were mainly split by either occurring in random order or age-dependent . Types of chronic organ damage were identical in 8 of the families and different in 3 of the families. The same combination of chronic liver disease was found in 6 families and chronic liver disease complicated with neurological disease in 2 families. Split organ damage in siblings was found when an older sibling was complicated by neurological disease. There was no reverse combination of a younger sibling being complicated by neurological disease in any of the families. Phenotype combinations of siblings were mainly modified by externally-induced hemolytic episodes, while chronic organ damage in siblings was split by age-dependent neurological complications.
ATP7B基因的克隆证明威尔逊病是一种伴有多种肝外并发症的肝铜中毒。具有相同遗传背景且暴露于相似环境因素下的患病同胞可能是研究基因型-表型相关性的良好模型。从一个数据库中选取了11个家庭中的23名患病同胞。首先根据国际提议确定表型。对慢性器官损伤的最终类型进行重新评估以进行终身管理。5个家庭的表型相同，6个家庭的表型不同。在3名较年轻的同胞和1名较年长的同胞中发现了急性肝表型。所有人都在潜在慢性肝病的基础上挺过了急性溶血发作。其中1人还出现了神经系统疾病并发症。在1个家庭的2名年长同胞、3个家庭的1名较年长同胞和1个家庭的最年长同胞中发现了伴有神经精神症状和肝病的神经表型。同胞中的表型主要是随机出现或与年龄相关而出现差异。8个家庭的慢性器官损伤类型相同，3个家庭的不同。6个家庭出现相同的慢性肝病组合，2个家庭出现慢性肝病合并神经系统疾病。当较年长的同胞出现神经系统疾病并发症时，在同胞中发现了器官损伤的差异。在任何家庭中都没有出现较年轻的同胞出现神经系统疾病并发症的相反组合。同胞的表型组合主要由外部诱发的溶血发作改变，而同胞中的慢性器官损伤则因与年龄相关的神经系统并发症而出现差异。
