Genetic homogeneity of mutational spectrum of group-A xeroderma pigmentosum in Tunisian patients.
BACKGROUND
Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by cutaneous and ocular alterations. Eight genes, Xeroderma Pigmentosum group A (XPA) to Xeroderma Pigmentosum group G (XPG) and Xeroderma Pigmentosum group V (XPV), are known to be responsible for the disease and products of these genes are involved in the repair of deoxyribonucleic acid (DNA) lesions generated by UV radiation. Several XP patients suffer from neurological defects, found in the XPA (the most common form), D and G groups. The aim of this study was to investigate the mutational spectrum of XPA in Tunisia, in order to propose a simple tool for molecular diagnosis.


METHODS
This study was carried out on six unrelated families with nine Tunisian XPA patients. Clinical features were recorded. As a previous study showed the presence of the R228X mutation in Tunisia, patients were first screened for this mutation by polymerase chain reaction-restriction fragment length polymorphism and then confirmed by direct sequencing.


RESULTS
The results showed that all patients carried the XPA R228X mutation. This mutation corresponds to a C to T transition, which creates a premature stop codon at position 228, thus causing a DNA repair defect.


CONCLUSIONS
The XPA R228X mutation is common in Tunisian population. This mutation is associated with a relatively moderate phenotype of the XPA. As all explored patients presented the recurrent mutation XPA R228X, a potential founder effect was searched and confirmed by haplotype analysis. Taking into account similar genetic background, investigation of this mutation should allow a cost effective and rapid diagnosis of XPA in north-African populations.
Molecular Investigation of Genetic Orphan Diseases Research Unit, Pasteur Institute of Tunis, Tunis, Tunisia.
Olfa
O
Messaoud
Mariem
M
Ben Rekaya
Wafa
W
Cherif
Faten
F
Talmoudi
Hammouda
H
Boussen
Inçaf
I
Mokhtar
Samir
S
Boubaker
Ahlem
A
Amouri
Sonia
S
Abdelhak
Mohamed
M
Zghal
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D017354:Point Mutation; D014416:Tunisia; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics; D055815:Young Adult
D051760:Xeroderma Pigmentosum Group A Protein