Original articles

Charfeddine, Chérine; Mokni, M.; Mousli, R. Ben; El-Kares, Reyhan; Bouchlaka, Chiraz; Boubaker, Samir; Ghedamsi, S.; Baccouche, D.; Osman, A. Ben; Dellagi, Koussay; Abdelhak, Sonia

doi:10.1111/j.1365-2133.2003.05606.x

Cited by 43 publications

(10 citation statements)

References 27 publications

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“…Indeed, the p.C99Y mutation responsible for MDM is distributed in various geographic areas of the country, while the p.C77R mutation is restricted to the North. On the other hand, the c.82delT mutation is widely encountered in populations from the Mediterranean basin and also in Scottish and Croatian ones [37,73]. …”

Section: Resultsmentioning

confidence: 99%

“…A possible explanation for this observation is the selective advantage of heterozygous in the case of recessive disorders [75,81]. The existence of multiple founder mutations affecting the same gene exclusively in the Tunisian population as in the case of Acrodermatitis enteropathica [82] and MDM [73] could be explained by an autochtonous mutational event. As these diseases have not yet been investigated in the neighboring countries, specificity of the mutations to Tunisian population should be taken cautiously.…”

Section: Discussionmentioning

confidence: 99%

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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by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory.ResultsWe identified two different classes of founder mutations.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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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“…Mutation analysis was carried out in the affected members. All exons of the SLURP-1 gene with adjacent sequences of exon-intron borders were amplified by PCR with primers and conditions described previously [4]. Mutation screening was performed by direct sequencing using Big Dye terminator technology (ABI 3130), and sequences were analyzed using Bioedit packages.…”

Section: Methodsmentioning

confidence: 99%

“…Meleda refers to an Adriatic island of the Dalmatia region of Croatia, where the occurrence of the disease as an entity of its own among the various forms of Keratosis palmoplantaris hereditaria was first described [2]. The largest MDM series were reported from North Africa: Tunisia (11 families with 45 patients) and Algeria (16 families with 21 patients) [3, 4]. MDM is characterized by erythema and hyperkeratosis of the palms and soles, extending to the dorsal aspects of the hands and feet (known as transgrediens) and perioral erythema and psoriasiform plaques on the elbows and knees.…”

Section: Introductionmentioning

confidence: 99%

Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region

Bchetnia

Laroussi

Youssef

et al. 2013

BioMed Research International

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Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

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“…A polymerase chain reaction (PCR) test was carried out as described by Charfeddine et al . [13]. The PCR template was sequenced using an ABI 3130 automated sequencing system (Applied Biosystems, California, USA).…”

Section: Case Presentationmentioning

confidence: 99%

Coexistence of mal de Meleda and congenital cataract in a consanguineous Tunisian family: two case reports

et al. 2010

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IntroductionMal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts.Case presentationA Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family.ConclusionTo the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda.

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Original articles

Abstract: The results suggest that the ARS gene is likely to be responsible for MDM in the eight Tunisian families. The clinical variability in the expression of PPK in MDM Tunisian patients might be accounted for by the intervention of modifier genes influencing the MDM phenotype.

Cited by 43 publications

References 27 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

Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region

Coexistence of mal de Meleda and congenital cataract in a consanguineous Tunisian family: two case reports

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