Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations

Bouchlaka, Chiraz; Abdelhak, Sonia; Amouri, Ahlem; Abid, Abdelmajid; Hadiji, S.; Frikha, M.; Othman, Tarek Ben; Amri, Fethi; Ayadi, Hammadi; Hachicha, M.; Rebaï, Ahmed; Saâd, Ali; Dellagi, Koussay

doi:10.1007/s10038-003-0037-z

Cited by 40 publications

(44 citation statements)

References 60 publications

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“…The present study demonstrates that, in spite of the high rate of endogamous marriages in Tunisia, there was a genetic and a mutational heterogeneity affecting the Tunisian MGA1 patients, confirming previous data on several Mendelian diseases affecting the Tunisian population (Elloumi-Zghal et al 2002;Bouchlaka et al 2003, Charfeddine et al 2003). The characterization of new genes and new mutations responsible for MGA1 will, in the future, yield new biological insights and a better comprehension of all the steps involved in the transport of Vit B12 and also facilitate a more exact diagnosis of new suspected cases at an earlier stage of the disease, which is important for the appropriate treatment.…”

Section: Discussionsupporting

confidence: 91%

Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients

Bouchlaka

Maktouf

Mahjoub³

et al. 2007

J Hum Genet

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Megaloblastic anaemia 1 (MGA1) is a rare autosomal recessive condition characterized by selective intestinal vitamin B12 malabsorption and proteinuria. More than 200 MGA1 patients have been identified worldwide, but the disease is relatively prevalent in Finland, Norway and several Eastern Mediterranean regions. MGA1 is genetically heterogeneous and can be caused by mutations in either the cubilin (CUBN) or the amnionless (AMN) gene. In the present study we investigated the molecular defect underlying MGA1 in nine Tunisian patients belonging to six unrelated consanguineous families. Haplotype and linkage analyses, using microsatellite markers surrounding both CUBN and AMN genes, indicated that four out of the six families were likely to be linked to the CUBN gene. Patients from these families were screened for the Finnish, Mediterranean and Arabian mutations already published. None of the screened mutations could be detected in our population. One family showed a linkage to AMN gene. Direct screening of the AMN gene allowed the identification of the c.208-2A>G mutation, previously described in a Jewish Israeli patient of Tunisian origin and in Turkish patients. This suggests that the c.208-2A>G mutation may derive from a single Mediterranean founder ancestor. For the last family, haplotype analysis excluded both CUBN and AMN genes, suggesting the existence of a third locus that may cause MGA1.

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Section: Discussionsupporting

confidence: 91%

Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients

Bouchlaka

Maktouf

Mahjoub³

et al. 2007

J Hum Genet

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“…These findings further delineate the genetic heterogeneity of rare autosomal recessive diseases in Tunisia, as reported previously for different conditions. [22][23][24][25][26] Compared with the other two genes known to cause achromatopsia CNGA3 and CNGB3, GNAT2 is only a minor achromatopsia locus, which account for 2% of the cases. 7 As this is the largest sibship affected with GNAT2 achromatopsia, this family gave a unique opportunity for phenotype-genotype analysis and comparison to other complete achromatopsia subtypes.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene

Ouechtati

Merdassi²,

Bouyacoub

et al. 2010

J Hum Genet

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Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119À69G4C, c.161+66A4T and c.875À31G4C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

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“…Thus, the number of different pathogenic variants described for the FANCA gene is very high considering the relatively low number of patients. [9][10][11][12][13][14] Mutation type is also heterogeneous, including point mutations, small insertions/ deletions, splicing mutations, and large intragenic deletions. Therefore, it is necessary to combine several methodologies for mutation screening.…”

Section: Introductionmentioning

confidence: 99%