High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis

Rekaya, Mariem Ben; Messaoud, Olfa; Talmoudi, Faten; Nouira, Saïd; Ouragini, Houyem; Amouri, Ahlem; Boussen, Hamouda; Boubaker, Samir; Mokni, M.; Mokthar, I; Abdelhak, Sonia; Zghal, M.

doi:10.1038/jhg.2009.50

Cited by 45 publications

(49 citation statements)

References 20 publications

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“…The common XPC mutation, c.1643_1644delTG (p.Val548AlafsX25), present at the homozygous state in 87% of XP-C patients, has been previously reported in 24 XP-C patients; 21 homozygous patients originated from North Africa mainly Tunisia (Li et al, 1993;Khan et al, 2006;Mahindra et al, 2008, Ben Rekaya et al, 2009, and three patients from Italy, Egypt, and Africa, respectively (Chavanne et al, 2000;Ridley et al, 2005). Two heterozygous patients (XP132BE and XP30BE) originated from USA and Honduras (Khan et al, 2006).…”

Section: Discussionmentioning

confidence: 92%

A Prevalent Mutation with Founder Effect in Xeroderma Pigmentosum Group C from North Africa

Soufir

Ged

Bourillon

et al. 2010

Journal of Investigative Dermatology

144

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Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that is associated with an inherited defect of the nucleotide excision repair pathway (NER). In this study, we investigated the involvement of XP genes in 86 XP patients belonging to 66 unrelated families, most of them consanguineous and originating from Maghreb. Sequencing analysis was performed either directly (44 probands) or after having previously characterized the involved XP gene by complementation assay (22 families). XPC and XPA mutations were respectively present in 56/66 and 8/66 probands. Strikingly, we identified the same homozygous frameshift mutation c.1643_1644delTG (p.Val548AlafsX25) in 87% of XP-C patients. Haplotype analysis showed a common founder effect for this mutation in the Mediterranean region, with an estimated age of 50 generations or 1,250 years. Among 7/8 XP-A patients, we found the previously reported nonsense homozygous XPA mutation (p.Arg228X). Six mutations--to our knowledge previously unreported--(five in XPC, one in XPA) were also identified. In conclusion, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. As the (p.Val548AlafsX25) XPC mutation is responsible for a huge proportion of XP cases, our data imply an obvious simplification of XP molecular diagnosis, at least in North Africa.

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Section: Discussionmentioning

confidence: 92%

A Prevalent Mutation with Founder Effect in Xeroderma Pigmentosum Group C from North Africa

Soufir

Ged

Bourillon

et al. 2010

Journal of Investigative Dermatology

144

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“…Screening for mutations was performed by direct sequencing as previously described [3,4,6] and maternal-foetal contamination was checked by genotyping using the Identifiler Kit (Applied Biosystems). Genotyping for 16 polymorphic microsatellite markers (15 autosomal and 1 located on the X chromosome) were determined for the mother, the father and the foetus.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported the presence of 2 founder mutations among Tunisian XP patients: XPC p.V548AfsX25 [3] and XPA p.R228X [4]. Nevertheless, the emergence of private mutations has also been noted [5,6].…”

Section: Introductionmentioning

confidence: 99%

The Experience of a Tunisian Referral Centre in Prenatal Diagnosis of <b><i>Xeroderma pigmentosum</i></b>

Messaoud

Rekaya

Jerbi

et al. 2013

Public Health Genomics

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Aims: Xeroderma pigmentosum (XP, OMIM 278700-278780) is one of the most severe genodermatoses and is relatively frequent in Tunisia. In the absence of any therapy and to better manage the disease, we aimed to develop a molecular tool for DNA-based prenatal diagnosis. Methods: Six consanguineous Tunisian XP families (4 XP-A and 2 XP-C) have benefited from a prenatal diagnosis. Screening for mutations was performed by direct sequencing, while maternal-foetal contamination was checked by genotyping. Results: Among the 7 prenatal diagnoses, 4 foetuses were heterozygous for the screened mutation. Exclusion of contamination by maternal cells was checked. Mutations were detected at a homozygous state in the remaining cases, and the parents decided to terminate pregnancy. Conclusion: Our study illustrates the implementation of prenatal diagnosis for better health support of XP in Tunisia.

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“…In several studies, XP complementation group C ( XPC ) is the major disease-causing gene with a recurrent mutation in the Mediterranean region [5, 6]. According to these findings, the Department of Medical Genetics in Rabat recommends the molecular diagnosis of XP by screening for the recurrent mutation: c.1643_1644delTG (p.Val548AlafsX25) in the XPC gene.…”

Section: Introductionmentioning

confidence: 99%

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report

et al. 2017

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BackgroundXeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa. According to these findings, the Department of Medical Genetics in Rabat offers molecular diagnosis by screening for the recurrent mutation c.1643_1644delTG which represents 74% of all the probands with xeroderma pigmentosum.Case presentationWe describe the case of a 21-year-old Moroccan son of consanguineous parents diagnosed with xeroderma pigmentosum on the basis of sun-exposed skin abnormalities and bilateral ocular involvement.A molecular study led to the identification of a new frameshift insertion of four nucleotides in exon 9.ConclusionsTo the best of our knowledge, this mutation has not been described. The sequencing of the ninth exon should be proposed as first line molecular analysis for all Moroccan patients with xeroderma pigmentosum.

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High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis

Cited by 45 publications

References 20 publications

A Prevalent Mutation with Founder Effect in Xeroderma Pigmentosum Group C from North Africa

A Prevalent Mutation with Founder Effect in Xeroderma Pigmentosum Group C from North Africa

The Experience of a Tunisian Referral Centre in Prenatal Diagnosis of <b><i>Xeroderma pigmentosum</i></b>

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report

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