Prevalence of Wilson disease based on genome databases in Japan

Abstract

Background Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene. In 1984, Scheinberg and Sternlieb estimated the prevalence of WD to be 1:30 000. However, recent epidemiological studies have reported increasing prevalence rates in different populations. The carrier frequency of ATP7B variants and the prevalence of WD in the Japanese population have not been reported using multiple databases. Methods Multiple public databases were used. First, we included mutations in the ATP7B gene that were registered in the Human Gene Mutation Database (HGMD) Professional, where 885 ATP7B variants were identified as pathogenic. Next, we investigated the allele frequencies of these 885 variants in Japanese individuals using the Human Genetic Variation Database (HGVD) and the Japanese Multi Omics Reference Panel (jMorp). Results Of the 885 variants of ATP7B, 7 and 12 missense and nonsense variants, zero and three splicing variants, and zero and two small deletions were found in the HGVD and in jMorp, respectively. The total allele frequencies of the ATP7B mutations were 0.011 in the HGVD and 0.014 in the jMorp. According to these data, the carrier frequencies were 0.022 (2.2%) and 0.028 (2.8%), respectively, and patient frequencies were 0.000121 (1.21/10 000 individuals) and 0.000196 (1.96/10 000 individuals), respectively. Conclusions This is the first study to report the carrier frequency of ATP7B variants and the prevalence of WD in Japan using multiple databases. The calculated prevalence of WD was comparatively higher than that of previous reports, indicating previous underdiagnosis or the existence of less severe phenotypes.

Initial Assessment Findings in Patients With Confirmed Wilson’s Disease

“…Оригинальные исследования деляет разнообразие манифестации и течения БВК [5][6][7][8][9]. По данным К. У. Вильчука и соавт.…”

“…В последние годы наблюдается интерес к проблеме БВК, что подтверждается количеством публикаций в ведущих мировых журналах. Результаты популяционных и генетических исследований свидетельствуют о том, что БВК уже не может рассматриваться как редкое заболевание [5][6][7][8][9][10].…”

Nomogram-based prediction of portal vein system thrombosis formation after splenectomy in patients with hepatolenticular degeneration

“…The prevalence of HLD in South Korea is 38.7 per million. In Japan, it is estimated to be 1.21/10,000 to 1.96/10,000 based on the mutation of ATP7B (5,6). In a recent study, 1,533,370 people were investigated in Anhui Province, China, and nine cases of HLD were found, with an estimated incidence of 17.93 per million (7).…”

The Role of Zinc in the Treatment of Wilson’s Disease

“…In a study of 1172 WD index patients, no correlation with disease phenotype was identified, of which 40% were heterozygotes and 39% were compound heterozygotes, while in 21%, only one mutation was found [ 8 ]. Incidence is usually quoted as 1:30,000 [ 13 , 14 ], but recent genetic studies have shown a higher prevalence, ranging from 1:2400 and 1:3150 to 1:6500 to 1:20,000 if all, only pathogenic, and suspected low penetrance of variants are included, respectively [ 12 , 15 , 16 ]. The discrepancy between the diagnostic rates and hypothesized genetic prevalence could be attributed to either a combination of low penetrance and/or low rates of diagnosis.…”