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Article Dans Une Revue Journal of Investigative Dermatology Année : 2010

A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa.

Nadem Soufir
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Cecile Ged
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Agnes Bourillon
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Cécile Chemin
Anne Stary
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Jacques Armier
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Daniele Pham
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Khadija Khadir
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Smail Hadj-Rabia
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Hubert de Verneuil
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Hakima Benchiki
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Alain Sarasin
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Résumé

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.

Dates et versions

hal-00549153 , version 1 (21-12-2010)

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Nadem Soufir, Cecile Ged, Agnes Bourillon, Frederic Austerlitz, Cécile Chemin, et al.. A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa.. Journal of Investigative Dermatology, 2010, 130 (6), pp.1537-42. ⟨10.1038/jid.2009.409⟩. ⟨hal-00549153⟩
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