Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups

Kalinsky, Hagar; Funes, Adina; Zeldin, Alina; Pel‐Or, Yehuda; Korostishevsky, Michael; Gershoni‐Baruch, Ruth; Farrer, Lindsay A.; Bonné‐Tamir, Batsheva

doi:10.1002/(sici)1098-1004(1998)11:2<145::aid-humu7>3.3.co;2-f

Cited by 6 publications

(9 citation statements)

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“…The frequent mutations that are prevalent in several ethnic groups are given in Table 3. The identification of 50% homozygous mutations in the Saudi WD patients is consistent with other published findings that showed the mutation detection in each ethnic group varied from 48 to 70% (Loudianos et al, 1996;Shah et al, 1997;Kalinsky et al, 1998;Curtis et al, 1999;Wu et al, 2001). Failure to detect any mutation(s) in the remaining Saudi WD patients might be explained by (i) the presence of mutations outside the open reading frame of the gene, i.e.…”

Section: Discussionsupporting

confidence: 89%

“…Its incidence was estimated at 30 per million in USA, Germany and Japan (Sheinberg and Sternlieb, 1984). It is more common (1 in 3000-10 000) in communities where consanguineous marriages are prevalent such as the Druze, Yemenite and Iranian Jews, and Palestinians (Kalinsky et al, 1998). Very few cases were described in Saudi Arabia (Bahemulka et al, 1988;Nazer et al, 1993;Majumdar et al, 2000), where consanguineous marriages exceed 50% (Al Rajeh et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi‐specific mutations

Jumah¹,

Majumdar²,

Rajeh³

et al. 2004

Euro J of Neurology

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Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi‐specific mutations

Jumah¹,

Majumdar²,

Rajeh³

et al. 2004

Euro J of Neurology

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“…Interestingly, the Met645Arg mutation was previously reported to be present only in Ashkenazi Jews. 8 It is well documented that, on their way to the American continent, many Jews settled in the Canary Islands escaping the Inquisition. Thus, it is possible that this mutation was introduced by one of these groups.…”

Section: Genetics Of Wd In the Island Of Gran Canariamentioning

confidence: 99%

“…5,6 However, most of the other mutations appear at low frequency and are generally associated with specific ethnic groups. [5][6][7][8][9][10] Several attempts have been made to correlate the presence of specific mutations with the phenotypic characteristics of the disease. These include age of onset, hepatic and neurological presentations, presence of KF rings, and ceruloplasmin serum levels.…”

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High Prevalence of the Very Rare Wilson Disease Gene Mutation Leu708pro in the Island of Gran Canaria (Canary Islands, Spain): A Genetic and Clinical Study

García-Villarreal

Daniels²,

Shaw³

et al. 2000

Hepatology

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The molecular basis of Wilson disease (WD), an autosomal recessive disorder, is the presence of mutations in the ATP7B gene, a copper transporting ATPase. Hospital records indicated a higher prevalence of WD (1 in 2,600) in some counties in the northeastern region of the island of Gran Canaria (Canary Islands, Spain) that was around 10-fold higher than that described for European populations (1 in 30,000). The ATP7B gene was analyzed for mutations in 24 affected subjects, revealing a high prevalence of the rare Leu708Pro mutation present in 12 homozygous and 7 heterozygous individuals. In these patients, who constitute one of the largest described cohorts of WD homozygotes, we found a variable clinical presentation of the disease, although the biochemical picture was homogenous and characteristic, thereby confirming that the Leu708Pro change is indeed a mutation associated with WD. Haplotype analysis of subjects homozygous for the Leu708Pro mutation showed a conserved shared region smaller than 1 centimorgan (cM), and the region of linkage disequilibrium between the Leu708Pro mutation and neighboring microsatellite markers extended approximately 4.6 cM. When comparing the amount of linkage disequilibrium versus genetic distance from the disease mutation, it was estimated that a common ancestral Leu708Pro chromosome may have been introduced in Gran Canaria over 56 generations ago, dating it back to pre-Hispanic times. The prevalence, and the tight geographical distribution of the Leu708Pro chromosome suggests that the Canary Islands can be considered a genetic isolate for linkage disequilibrium studies.

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Mutational analysis of ATP7B and genotype–phenotype correlation in Japanese with Wilson's disease

et al. 2000

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The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A). Various mutations of ATP7B have been identified. This study aimed to detect disease-causing mutations, to clarify their frequency and distribution, to determine whether genotype correlates with phenotype, and to determine the rate of abnormal findings in heterozygotes for the WD gene. We analyzed 41 unrelated Japanese WD families, including 47 patients. Twenty-one mutations, including nine novel ones, were identified. 2871delC (15.9%), 1708-5T-->G (11. 0%), and Arg778Leu (13.4%) were the most common mutations. 2871delC was detected mainly in eastern Japan and 1708-5T-->G in western Japan. The homozygotes for the 1708-5T-->G, 2871delC, or Arg778Leu mutations did not show a correlation with their phenotypes. Ceruloplasmin and copper levels were abnormally low in 28.6% and 35. 0% of heterozygotes, respectively. When patients and their families are screened for WD, a high rate of abnormal laboratory data in heterozygotes must be taken into account.

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Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups

Cited by 6 publications

References 0 publications

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi‐specific mutations

A clinical and genetic study of 56 Saudi Wilson disease patients: identification of Saudi‐specific mutations

High Prevalence of the Very Rare Wilson Disease Gene Mutation Leu708pro in the Island of Gran Canaria (Canary Islands, Spain): A Genetic and Clinical Study

Mutational analysis of ATP7B and genotype–phenotype correlation in Japanese with Wilson's disease

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