title: History of settlement of villages from Central Tunisia by studying families sharing a common founder Glycogenosis type III mutation.
abstract: Glycogen storage disease type III (GSD III; Cori disease; Forbes disease) is an autosomal recessive inherited metabolic disorder resulting from deficient glycogen debrancher enzyme activity in liver and muscle. In this study, we focused on a single AGL gene mutation p.W1327X in 16 Tunisian patients from rural area surrounding the region of Mahdia in Central Tunisia. This constitutes the largest pool of patients with this mutation ever described. This study was performed to trace the history of the patients' ancestries in a single region. After extraction of genomic DNA, exon 31 of AGL gene was sequenced. The patients were investigated for the hypervariable segment 1 of mitochondrial DNA and 17 Y-STR markers. We found that the p.W1327X mutation was a founder mutation in Tunisia Analysis of maternal lineages shows an admixture of autochthonous North African, sub-Saharan and a predominance of Eurasian haplogroups. Heterogeneity of maternal haplogroups indicates an ancient settlement. However, paternal gene flow was highly homogeneous and originates from the Near East. We hypothesize that the p.W1327X mutation was introduced into the Tunisian population probably by a recent migration event; then the mutation was fixed in a small region due to the high rate of consanguineous marriages and genetic drift. The screening for this mutation should be performed in priority for GSD III molecular diagnosis, for patients from the region of Mahdia and those from regions sharing the same settlement history.
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Faten Ben
authors.initials: FB
authors.lastname: Rhouma
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Habib
authors.initials: H
authors.lastname: Messai
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Sana
authors.initials: S
authors.lastname: Hsouna
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Nizar Ben
authors.initials: NB
authors.lastname: Halim
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Wafa
authors.initials: W
authors.lastname: Cherif
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Sihem Ben
authors.initials: SB
authors.lastname: Fadhel
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Afaf
authors.initials: A
authors.lastname: Tiar
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Majdi
authors.initials: M
authors.lastname: Nagara
authors.affiliation: c Département de Pédiatrie , Hôpital La Rabta de Tunis, Unité des maladies métaboliques héréditaires , Tunis , Tunisia .|d Faculté de Médecine de Tunis , Tunis , Tunisia , and.
authors.forename: Hatem
authors.initials: H
authors.lastname: Azzouz
authors.affiliation: e Département de Pédiatrie , Hôpital Tahar Sfar , Mahdia , Tunisia.
authors.forename: Mohamed-Tahar
authors.initials: MT
authors.lastname: Sfar
authors.affiliation: c Département de Pédiatrie , Hôpital La Rabta de Tunis, Unité des maladies métaboliques héréditaires , Tunis , Tunisia .|d Faculté de Médecine de Tunis , Tunis , Tunisia , and.
authors.forename: Marie-Françoise Ben
authors.initials: MF
authors.lastname: Dridi
authors.affiliation: c Département de Pédiatrie , Hôpital La Rabta de Tunis, Unité des maladies métaboliques héréditaires , Tunis , Tunisia .|d Faculté de Médecine de Tunis , Tunis , Tunisia , and.
authors.forename: Neji
authors.initials: N
authors.lastname: Tebib
authors.affiliation: e Département de Pédiatrie , Hôpital Tahar Sfar , Mahdia , Tunisia.
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Ayadi
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.affiliation: a Institut Pasteur de Tunis, Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05 , Tunis , Tunisia .|b Université Tunis El Manar , Tunis , Tunisia .
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
mesh_terms: D003241:Consanguinity; D004272:DNA, Mitochondrial / Q000235:genetics; D018703:Founder Effect; D051456:Gene Flow; D040961:Genetic Drift; D018740:Genetic Heterogeneity; D006004:Glycogen Debranching Enzyme System / Q000235:genetics; D006010:Glycogen Storage Disease Type III / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes; D063426:Human Migration; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D012424:Rural Population; D014416:Tunisia
chemical_list: D004272:DNA, Mitochondrial; D006004:Glycogen Debranching Enzyme System
keywords: Consanguinity; gene flow; haplogroup; haplotype; p.W1327X