Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Gene. 2023 Dec 15;887:147728. doi: 10.1016/j.gene.2023.147728. Epub 2023 Aug 25.
Wilson disease is caused by pathogenic variants in the ATP7B gene which encodes a copper-transporting ATPase.
Describe a common founder pathogenic variant among Bukharan Jews and to assess its prevalence, clinical features, and outcome.
The cohort consisted of patients of Bukharan Jewish descent diagnosed with Wilson disease at a tertiary pediatric medical center in 2013-2018. Clinical and genetic data were collected and analyzed.
Six patients from 4 unrelated families who were homozygous for the c.3784G > T p.(Val1262Phe) pathogenic variant in ATP7B were identified. Five presented with elevated aminotransferase levels, and one, with acute liver failure. Mean age at diagnosis was 8.7 years (5-12.5). Serum ceruloplasmin level was extremely low in all patients (1.9-7 mg/dL; mean 3.2(. The variant was identified in a heterozygous state in 5/153 Bukharan Jews; 2/33 from our local exome database and 3/120 healthy unrelated Bukharan Jews in another cohort, for an estimated carrier frequency of ∼1:30.
We report a common founder pathogenic variant in the ATP7B gene among Bukharan Jews associated with severe early-onset Wilson disease. Given the clinical severity, high frequency of the variant, and being a treatable disease, its inclusion in pre-symptomatic screening in the Bukharan Jewish community should be considered. Furthermore, WD should be part of future genetic newborn screening programs in Israel and worldwide, to enable early treatment and prevention of future life-threatening complications.
威尔逊病是由 ATP7B 基因的致病变异引起的，该基因编码一种铜转运 ATP 酶。
描述布哈拉犹太人中一种常见的致病变异体，并评估其患病率、临床特征和结局。
该队列由 2013 年至 2018 年在一家三级儿科医学中心诊断为威尔逊病的布哈拉犹太裔患者组成。收集并分析了临床和遗传数据。
从 4 个无关的家庭中发现了 6 名纯合子携带 ATP7B 基因 c.3784G>T p.(Val1262Phe) 致病变异体的患者。5 名患者表现为转氨酶升高，1 名患者表现为急性肝衰竭。诊断时的平均年龄为 8.7 岁（5-12.5 岁）。所有患者的血清铜蓝蛋白水平极低（1.9-7mg/dL；平均 3.2）。该变异在 5/153 名布哈拉犹太人中以杂合状态存在；在我们的本地外显子组数据库中发现 2/33 例，在另一队列中的 120 名健康无关的布哈拉犹太人中发现 3/120 例，估计携带者频率约为 1:30。
我们报告了布哈拉犹太人中 ATP7B 基因的一种常见致病变异体，与严重的早发性威尔逊病有关。鉴于疾病的严重程度、变异体的高频率以及该病是一种可治疗的疾病，应考虑将其纳入布哈拉犹太社区的无症状筛查中。此外，威尔逊病应成为以色列和全球未来遗传新生儿筛查计划的一部分，以实现早期治疗和预防未来危及生命的并发症。
