title: Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients.
abstract: 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.
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis Belvédère, Tunisia.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Bouchlaka
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis Belvédère, Tunisia.|Nuclear Medicine Group, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Chokri
authors.initials: C
authors.lastname: Maktouf
authors.affiliation: Department of Paediatrics, C.H.U. Tahar Sfar, Mahdia, Tunisia.
authors.forename: Bahri
authors.initials: B
authors.lastname: Mahjoub
authors.affiliation: Department of Paediatrics, C.H.U. Tahar Sfar, Mahdia, Tunisia.
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Ayadi
authors.affiliation: Department of Paediatrics, C.H.U. Tahar Sfar, Mahdia, Tunisia.
authors.forename: M Tahar
authors.initials: MT
authors.lastname: Sfar
authors.affiliation: Department of Paediatrics, Hôpital d'Enfants, Tunis, Tunisia.
authors.forename: Mahbouba
authors.initials: M
authors.lastname: Sioud
authors.affiliation: Department of Paediatrics, C.H.U., Monastir, Tunisia.
authors.forename: Neji
authors.initials: N
authors.lastname: Gueddich
authors.affiliation: Department of Haematology, C.H.U., Aziza Othmana, Tunis, Tunisia.
authors.forename: Zouheir
authors.initials: Z
authors.lastname: Belhadjali
authors.affiliation: Centre de Biotechnologie de Sfax, Sfax, Tunisia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rebaï
authors.affiliation: Molecular Investigation of Genetic Orphan Diseases, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur 1002, Tunis Belvédère, Tunisia. sonia.abdelhak@pasteur.rns.tn.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Department of Haematology and Laboratory of Immunology, Vaccinology and Molecular Genetics, Institut Pasteur de Tunis, Tunis, Tunisia.
authors.forename: Koussay
authors.initials: K
authors.lastname: Dellagi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000749:Anemia, Megaloblastic / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D014416:Tunisia
chemical_list: D005819:Genetic Markers