title: A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa.
abstract: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that is associated with an inherited defect of the nucleotide excision repair pathway (NER). In this study, we investigated the involvement of XP genes in 86 XP patients belonging to 66 unrelated families, most of them consanguineous and originating from Maghreb. Sequencing analysis was performed either directly (44 probands) or after having previously characterized the involved XP gene by complementation assay (22 families). XPC and XPA mutations were respectively present in 56/66 and 8/66 probands. Strikingly, we identified the same homozygous frameshift mutation c.1643_1644delTG (p.Val548AlafsX25) in 87% of XP-C patients. Haplotype analysis showed a common founder effect for this mutation in the Mediterranean region, with an estimated age of 50 generations or 1,250 years. Among 7/8 XP-A patients, we found the previously reported nonsense homozygous XPA mutation (p.Arg228X). Six mutations--to our knowledge previously unreported--(five in XPC, one in XPA) were also identified. In conclusion, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. As the (p.Val548AlafsX25) XPC mutation is responsible for a huge proportion of XP cases, our data imply an obvious simplification of XP molecular diagnosis, at least in North Africa.
authors.affiliation: Laboratoire de Biochimie hormonale et génétique, Hôpital Bichat, APHP, Université Paris VII, 46 Rue Henri Huchard, Paris, France. nsoufir@yahoo.com
authors.forename: Nadem
authors.initials: N
authors.lastname: Soufir
authors.forename: Cecile
authors.initials: C
authors.lastname: Ged
authors.forename: Agnes
authors.initials: A
authors.lastname: Bourillon
authors.forename: Frederic
authors.initials: F
authors.lastname: Austerlitz
authors.forename: Cécile
authors.initials: C
authors.lastname: Chemin
authors.forename: Anne
authors.initials: A
authors.lastname: Stary
authors.forename: Jacques
authors.initials: J
authors.lastname: Armier
authors.forename: Daniele
authors.initials: D
authors.lastname: Pham
authors.forename: Khadija
authors.initials: K
authors.lastname: Khadir
authors.forename: Joelle
authors.initials: J
authors.lastname: Roume
authors.forename: Smail
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: Bakar
authors.initials: B
authors.lastname: Bouadjar
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.forename: Hubert
authors.initials: H
authors.lastname: de Verneuil
authors.forename: Hakima
authors.initials: H
authors.lastname: Benchiki
authors.forename: Bernard
authors.initials: B
authors.lastname: Grandchamp
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
mesh_terms: D000293:Adolescent; D000328:Adult; D000352:Africa, Northern / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D014983:Xeroderma Pigmentosum / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; C086984:XPC protein, human