Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

Messaoud, Olfa; Rekaya, Mariem Ben; Cherif, Wafa; Talmoudi, Faten; Boussen, H; Mokhtar, I.; Boubaker, Samir; Amouri, Ahlem; Abdelhak, Sonia; Zghal, M.

doi:10.1111/j.1365-4632.2010.04421.x

Cited by 23 publications

(18 citation statements)

References 17 publications

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“…The same picture is also shown for the major founder mutation p.R228X in xeroderma pigmentosum group A. Another private mutation was recently reported in one family [39,79]. In the second observation, more than one frequent mutation is responsible for the genetic disease.…”

Section: Discussionsupporting

confidence: 69%

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Romdhane

Kéfi

Azaiez

et al. 2012

Orphanet J Rare Dis

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BackgroundTunisia is a North African country of 10 million inhabitants. The native background population is Berber. However, throughout its history, Tunisia has been the site of invasions and migratory waves of allogenic populations and ethnic groups such as Phoenicians, Romans, Vandals, Arabs, Ottomans and French. Like neighbouring and Middle Eastern countries, the Tunisian population shows a relatively high rate of consanguinity and endogamy that favor expression of recessive genetic disorders at relatively high rates. Many factors could contribute to the recurrence of monogenic morbid trait expression. Among them, founder mutations that arise in one ancestral individual and diffuse through generations in isolated communities.MethodWe report here on founder mutations in the Tunisian population by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory.ResultsWe identified two different classes of founder mutations. The first includes founder mutations so far reported only among Tunisians that are responsible for 30 genetic diseases. The second group represents founder haplotypes described in 51 inherited conditions that occur among Tunisians and are also shared with other North African and Middle Eastern countries. Several heavily disabilitating diseases are caused by recessive founder mutations. They include, among others, neuromuscular diseases such as congenital muscular dystrophy and spastic paraglegia and also severe genodermatoses such as dystrophic epidermolysis bullosa and xeroderma pigmentosa.ConclusionThis report provides informations on founder mutations for 73 genetic diseases either specific to Tunisians or shared by other populations. Taking into account the relatively high number and frequency of genetic diseases in the region and the limited resources, screening for these founder mutations should provide a rapid and cost effective tool for molecular diagnosis. Indeed, our report should help designing appropriate measures for carrier screening, better evaluation of diseases burden and setting up of preventive measures at the regional level.

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Section: Discussionsupporting

confidence: 69%

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Romdhane

Kéfi

Azaiez

et al. 2012

Orphanet J Rare Dis

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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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“…This high frequency might be due to the high rate of consanguinity in Tunisia (29.8%) especially among families with autosomal recessive diseases (78.4%) [7] and to founder effects reported in XPC [8], XPA [9], and XPV genes (unpublished data) in the Tunisian population.…”

Section: Introductionmentioning

confidence: 99%

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

Rekaya

Jerbi

Messaoud

et al. 2013

BioMed Research International

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Xeroderma Pigmentosum (XP) is a rare recessive autosomal cancer prone disease, characterized by UV hypersensitivity and early appearance of cutaneous and ocular malignancies. We investigated four unrelated patients suspected to be XP-C. To confirm linkage to XPC gene, genotyping and direct sequencing of XPC gene were performed. Pathogenic effect of novel mutations was confirmed by reverse Transciptase PCR. Mutation screening revealed the presence of two novel mutations g.18246G>A and g.18810G>T in the XPC gene (NG_011763.1). The first is present in one patient XP50NEF, but the second is present in three unrelated patients (XP16KEB, XP28SFA, and XP45GB). These 3 patients are from three different cities of Southern Tunisia and bear the same haplotype, suggesting a founder effect. Reverse Transciptase PCR revealed the absence of the XPC mRNA. In Tunisia, as observed in an other severe genodermatosis, the mutational spectrum of XP-C group seems to be homogeneous with some clusters of heterogeneity that should be taken into account to improve molecular diagnosis of this disease.

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Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

Cited by 23 publications

References 17 publications

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

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

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

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