title: Further evidence of mutational heterogeneity of the XPC gene in Tunisian families: a spectrum of private and ethnic specific mutations.
abstract: 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.
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, LR 11 IPT 05, Institut Pasteur de Tunis and Université de Tunis El Manar, El Manar I, 2092 Tunis, Tunisia. rekayamariem@yahoo.fr
authors.forename: Mariem
authors.initials: M
authors.lastname: Ben Rekaya
authors.forename: Manel
authors.initials: M
authors.lastname: Jerbi
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.forename: Ahlem Sabrine
authors.initials: AS
authors.lastname: Ben Brick
authors.forename: Mohamed
authors.initials: M
authors.lastname: Zghal
authors.forename: Chiraz
authors.initials: C
authors.lastname: Mbarek
authors.forename: Ashraf
authors.initials: A
authors.lastname: Chadli-Debbiche
authors.forename: Meriem
authors.initials: M
authors.lastname: Jones
authors.forename: Mourad
authors.initials: M
authors.lastname: Mokni
authors.forename: Hamouda
authors.initials: H
authors.lastname: Boussen
authors.forename: Mohamed Samir
authors.initials: MS
authors.lastname: Boubaker
authors.forename: Becima
authors.initials: B
authors.lastname: Fazaa
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005006:Ethnicity / Q000235:genetics*; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D014416:Tunisia; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human