Multiplex ARMS PCR to Detect 8 Common Mutations of ATP7B Gene in Patients With Wilson Disease

Dastsooz, Hassan; Imanieh, Mohammad Hadi; Dehghani, Seyed Mohsen; Haghighat, Mahmood; Moini, Maryam; Fardaei, Majid

doi:10.5812/hepatmon.8375

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…Seventeen articles were included and distributed as follows: Saudi Arabia[ 18 - 21 ], Egypt[ 12 , 22 - 24 ], Turkey[ 25 , 26 ], Iran[ 27 , 28 ], Oman[ 29 ] and Lebanon[ 6 , 13 , 14 , 30 ]. Two reports on WD from Iraq were not included, as they had no genotypic information.…”

Section: Resultsmentioning

confidence: 99%

Wilson’s disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

Barada

Haddad

Katerji

et al. 2017

WJG

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AIMTo determine the phenotypes and predominant disease-causing mutations in Lebanese patients with Wilson’s disease, as compared to regional non-European data.METHODSThe clinical profile of 36 patients diagnosed in Lebanon was studied and their mutations were determined by molecular testing. All patients underwent full physical exam, including ophthalmologic slit-lamp examination ultrasound imaging of the liver, as well as measurement of serum ceruloplasmin and 24-h urinary-Cu levels. In addition, genetic screening using PCR followed by sequencing to determine disease-causing mutations and polymorphisms in the ATP7B gene was carried on extracted DNA from patients and immediate family members. Our phenotypic-genotypic findings were then compared to reported mutations in Wilson’s disease patients from regional Arab and non-European countries.RESULTSPatients belonged to extended consanguineous families. The majority were homozygous for the disease-causing mutation, with no predominant mutation identified. The most common mutation, detected in 4 out of 13 families, involved the ATP hinge region and was present in patients from Lebanon, Egypt, Iran and Turkey. Otherwise, mutations in Lebanese patients and those of the region were scattered over 17 exons of ATP7B. While the homozygous exon 12 mutation Trp939Cys was only detected in patients from Lebanon but none from the regional countries, the worldwide common mutation H1069Q was not present in the Lebanese and was rare in the region. Pure hepatic phenotype was predominant in patients from both Lebanon and the region (25%-65%). Furthermore, the majority of patients, including those who were asymptomatic, had evidence of some hepatic dysfunction. Pure neurologic phenotype was rare.CONCLUSIONFindings do not support presence of a founder effect. Clinical and genetic screening is recommended for family members with index patients and unexplained hepatic dysfunction.

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Section: Resultsmentioning

confidence: 99%

Wilson’s disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

Barada

Haddad

Katerji

et al. 2017

WJG

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“…However, the molecular diagnosis of WD is not feasible and is expensive in the clinical laboratory due to varied types of ATP7B gene mutations (7,8). According to past massive mutation screenings, there are some mutation hotspots depending on different ethnic groups and geographic location (9,10).…”

Section: Discussionmentioning

confidence: 99%

Genetic and Clinical Analysis in a Cohort of Patients with Wilson's Disease in Southwestern China

Liu

Zhou

Guo

et al. 2015

Archives of Medical Research

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“…A variety of alternative methods can be used to detect common variants. The simplest is to detect them by PCR and restriction analysis, multiplex PCR or PCR-MassArray screening, [9][10][11] enabling detection of diseasecausing variants in up to 80% of patients of particular ethnic background. The proposed workflow (Fig.…”

Section: Methodsmentioning

confidence: 99%

Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?

Espinós

Ferenci

2020

JHEP Reports

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The diagnosis of Wilson disease is not always easy. For many patients, a combination of tests reflecting disturbed copper metabolism may be needed. Testing for ATP7B variants has become part of the routine diagnostic approach. The methods of genetic testing include analysis of the 21 coding exons and intronic flanking sequences, in which exons with recurrent variants would be prioritised depending on the mutation frequency in the local population. If sequencing the entire ATP7B gene cannot identify 2 variants and the suspicion for Wilson disease is high, after reviewing the clinical data, WES (whole-exome sequencing) or WGS (whole-genome sequencing) could be applied. A workflow based on the type and number of ATP7B variants responsible for Wilson disease is proposed. Genetic testing is indicated for confirmation of diagnosis, family screening, and screening of newborns and infants and in unclear cases suspected of suffering from Wilson disease. However, genetic testing is not a routine screening test for Wilson disease. If no additional variants can be identified, it can be assumed that other hereditary disorders may mimic Wilson disease (congenital disorders of glycosylation, MEDNIK syndrome, idiopathic or primary copper toxicoses).

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Multiplex ARMS PCR to Detect 8 Common Mutations of ATP7B Gene in Patients With Wilson Disease

Cited by 8 publications

References 21 publications

Wilson’s disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

Wilson’s disease in Lebanon and regional countries: Homozygosity and hepatic phenotype predominance

Genetic and Clinical Analysis in a Cohort of Patients with Wilson's Disease in Southwestern China

Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?

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