Liu Xiao-Qing, Zhang Ya-Fen, Liu Tze-Tze, Hsiao Kwang-Jen, Zhang Jian-Ming, Gu Xue-Fan, Bao Ke-Rong, Yu Li-Hua, Wang Mei-Xian
Department of Neurology, Xinhua Hospital, Shanghai Second Medical University, 1665 Kongjiang Rd, Shanghai 200092, China.
World J Gastroenterol. 2004 Feb 15;10(4):590-3. doi: 10.3748/wjg.v10.i4.590.
To determine the mutational characterization of P-type ATP7B gene and to explore the correlation of ATP7B genotype to phenotype in Chinese patients with Wilson disease (WD).
Seventy-five patients with WD from 72 no-kinship families, 44 males and 31 females, were enrolled in this study. The age of onset ranged from 4 to 39 years, <=18 years in 72 patients. Some exons of ATP7B gene mutations were analyzed in patients with WD by using biochemical methods, polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and DNA sequence analysis. A total of 778 coding regions were identified with restriction enzyme Msp I. The activity of Cu-ATPase was assessed by measuring inorganic phosphorus.
Sixty-six of 75 patients (88%) had with hepatic manifestations, 39 of them had only hepatic manifestations, 27 patients had hepatic and neurological manifestations or other symptoms at the same time (16 patients had associated neurological manifestation, 3 patients had osteopathy, 8 patients had other symptoms). Eight of the 75 patients (10.7%) had only neurological symptoms, one patient (5 years old) had no symptom. Twelve changing patterns were detected in ATP7B gene by DNA sequencing, including seven mutations (R778L, C656X, G943D, V1140A, V1106I V1216M and 1384del17), six polymorphisms (IVS4-5t/c, A2495G, C2310G, IVS18+6c/t and IVS20+5a/g). R778L occurred in 49/66 patients (74%) with hepatic manifestations, homozygosis of R778L in 16 patients, heterozygosity of R778L in 33 patients. V1106I mutation of ATP7B gene occurred in 2 patients with delaying onset of clinical symptoms. Cu-ATPase activity of three patients with known mutations (R778L/V1106I/A2495G, R778L/V1216M and R778L/R778L) were determined, and the activity of Cu-ATPase was decreased by 44.55%, 88.23% and 69.49% respectively.
1384del17bp is a novel mutation found in WD patients. R778L is the most common mutation of ATP7B gene. There is a correlation between R778L and hepatic manifestations in WD patient.
确定P型ATP7B基因的突变特征，并探讨中国肝豆状核变性（WD）患者ATP7B基因基因型与表型的相关性。
本研究纳入了来自72个无亲缘关系家庭的75例WD患者，其中男性44例，女性31例。发病年龄为4至39岁，72例患者年龄≤18岁。采用生化方法、聚合酶链反应-单链构象多态性（PCR-SSCP）和DNA序列分析对WD患者的ATP7B基因突变的一些外显子进行分析。用限制性内切酶Msp I共鉴定出778个编码区。通过测量无机磷评估铜-ATP酶的活性。
75例患者中有66例（88%）有肝脏表现，其中39例仅有肝脏表现，27例同时有肝脏和神经表现或其他症状（16例有相关神经表现，3例有骨病，8例有其他症状）。75例患者中有8例（10.7%）仅有神经症状，1例患者（5岁）无症状。通过DNA测序在ATP7B基因中检测到12种变化模式，包括7种突变（R778L、C656X、G943D、V1140A、V1106I、V1216M和1384del17），6种多态性（IVS4-5t/c、A2495G、C2310G、IVS18+6c/t和IVS20+5a/g）。R778L出现在49/66例有肝脏表现的患者中（74%），16例为R778L纯合子，33例为R778L杂合子。ATP7B基因的V1106I突变发生在2例临床症状延迟出现的患者中。测定了3例已知突变（R778L/V1106I/A2495G、R778L/V1216M和R778L/R778L）患者的铜-ATP酶活性，其铜-ATP酶活性分别降低了44.55%、88.23%和69.49%。
1384del17bp是在WD患者中发现的一种新突变。R778L是ATP7B基因最常见的突变。WD患者中R778L与肝脏表现之间存在相关性。
