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. 2014 Mar;2(2):160-5.
doi: 10.1002/mgg3.55. Epub 2014 Feb 5.

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis

Ahlem Amouri  1 , Faten Talmoudi  1 , Olfa Messaoud  2 , Catherine D d'Enghien  3 , Mariem B Rekaya  2 , Ines Allegui  2 , Héla Azaiez  2 , Rym Kefi  2 , Ahlem Abdelhak  2 , Sondes H Meseddi  4 , Lamia Torjemane  5 , Monia Ouederni  6 , Fethi Mellouli  6 , Héla B Abid  7 , Lamia Aissaoui  7 , Mohamed Bejaoui  6 , Tarek B Othmen  5 , Dominique S Lyonnet  8 , Jean Soulier  9 , Mongia Hachicha  10 , Koussay Dellagi  11 , Sonia Abdelhak  2 , Tunisian Fanconi  12
Affiliations

High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis

Ahlem Amouri et al. Mol Genet Genomic Med. 2014 Mar.

Abstract

Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.

Keywords: Exon 15 deletion; Fanconi anemia; MLPA; founder haplotype; founder mutation.

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Figures

Figure 1
Figure 1
Geographic distribution of the founder mutation in FANCA gene in Tunisia. Eighty-five percent of the families with exon 15 founder deletion in FANCA gene are from southern Tunisia especially from Sidi Bouzid and Gafsa regions. Families are represented by points.
Figure 2
Figure 2
Pedigrees, haplotype analysis and results of multiplex ligation-dependent probe amplification (MLPA) assay for FANCA gene. GF53/09, GF68/09 and GF07/11 patients are compound heterozygous as they bear the founder haplotype at a heterozygous state and MLPA analysis show exon 15 deletion in one allele. GF33/11 and GFEA/11 patients present the founder haplotype at a homozygous state and total absence of the peak corresponding to exon 15 was noted in MLPA profile. MLPA profile for the control individual shows absence of any copy number changes.
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