title: A founder large deletion mutation in Xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy.
abstract: Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Ben Rekaya
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Laroussi
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Messaoud
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia ; Département de Dermatologie, Hôpital Charles Nicolle de Tunis, 1006 Tunis, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Jones
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Manel
authors.initials: M
authors.lastname: Jerbi
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Chokri
authors.identifier: 0000-0002-5237-2573
authors.initials: C
authors.lastname: Naouali
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouyacoub
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Chargui
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia ; Département de Dermatologie, Hôpital Charles Nicolle de Tunis, 1006 Tunis, Tunisia.
authors.forename: Becima
authors.initials: B
authors.lastname: Fazaa
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia ; Département d'Anatomie-Pathologique Humaine et Expérimentale, Institut Pasteur de Tunis, 1002 Tunis, Tunisia.
authors.forename: Mohamed Samir
authors.initials: MS
authors.lastname: Boubaker
authors.affiliation: Département d'Oncologie Médicale, Hôpital Abderrahman Mami, 2080 Ariana, Tunisia.
authors.forename: Hamouda
authors.initials: H
authors.lastname: Boussen
authors.affiliation: Département d'Oncologie Médicale, Hôpital La Rabta de Tunis, 1007 Tunis, Tunisia.
authors.forename: Mourad
authors.initials: M
authors.lastname: Mokni
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: Département de Dermatologie, Hôpital Charles Nicolle de Tunis, 1006 Tunis, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Zghal
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia ; Département de Dermatologie, Hôpital Charles Nicolle de Tunis, 1006 Tunis, Tunisia.
authors.forename: Aida
authors.initials: A
authors.lastname: Khaled
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique (LR 11 IPT 05), Institut Pasteur de Tunis, Université de Tunis El Manar, El Manar I, BP 74, 13 Place Pasteur 1002 Tunis Belvédère, 2092 Tunis, Tunisia.
authors.forename: Houda
authors.initials: H
authors.lastname: Yacoub-Youssef
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005091:Exons; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017384:Sequence Deletion; D014416:Tunisia; D014983:Xeroderma Pigmentosum / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases