c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with xeroderma pigmentosum

Abstract

Xeroderma pigmentosum is a rare autosomal recessive disease characterized by hypersensitivity to UV light which is due to alterations of the nucleotide excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the disease. Among them, the XPC gene is known to be the most mutated in Mediterranean patients. The aim of this study was to determine the frequency of the most common XPC mutation and describe the clinical features of Moroccan patients with xeroderma pigmentosum. Twenty four patients belonging to 21 unrelated Moroccan families and 58 healthy subjects were investigated. After clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25) mutation in the XPC gene was performed by PCR and automated sequencing of exon 9 in all patients and controls. The molecular analysis showed that among the 24 patients, 17 were homozygous for the c.1643_1644delTG mutation and all their tested parents were heterozygous, whereas the others (7 patients) did not carry the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21 families). None of the 58 healthy individuals carried this mutation. In addition, clinical investigation showed that the majority of the patients bearing this mutation have the same clinical features. Our results revealed that the p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum in Moroccan families. This would have an important impact on improving management of patients and their relatives.

Diagnosis ofXeroderma PigmentosumGroups A and C by Detection of Two Prevalent Mutations in West Algerian Population: A Rapid Genotyping Tool for the FrequentXPCMutation c.1643_1644delTG

“…Interestingly, Mahindra et al [ 41 ] also described the XPC mutation in two brother patients from North Sudan. Furthermore, the molecular analysis of 24 Moroccan patients showed that 17 were homozygous for the c.1643_1644delTG mutation [ 42 ]. Most XP-C African patients with delTG mutation in both alleles have similar clinical features consisting of photosensitivity, pigmentary lesions, and early onset of skin cancer without neurological involvement as our XP-C patients [ 22 , 39 , 41 ].…”

Further Evidence of Mutational Heterogeneity of theXPCGene in Tunisian Families: A Spectrum of Private and Ethnic Specific Mutations

“…This was confirmed by its high carriers frequency estimated to be 1/250 in Morocco [12]. Having a homogeneous mutational spectrum for the XPC gene has greatly simplified the molecular diagnosis of XP-C in the region [6, 8, 13]. Furthermore, two other private mutations have been recently reported in North African patients [6].…”

“…Molecular investigations of the XP-C group showed that it is the major group among the five North African countries called the Maghreb [6, 8, 12, 13]. Indeed, among the studied patients, about 87% of them shared the recurrent founder mutation c.1643_1644delTG (p.V548AlafsX25) [6].…”

The Moroccan Genetic Disease Database (MGDD): a database for DNA variations related to inherited disorders and disease susceptibility

“…13 The c.1643_1644delTG mutation in the XPC gene represents the major cause of xeroderma pigmentosum in Maghreb region (Morocco, Algeria and Tunisia); haplotype analysis revealed the presence of a common founder effect for this XPC mutation in the Mediterranean region. 14,15 The identification of founder mutations has important implications in molecular diagnosis and genetic counselling. Furthermore, a few prevalent founder mutations enable human geneticists to make more efficient genetic screening than testing for many rare mutations.…”