Diagnosis of Xeroderma Pigmentosum Groups A and C by Detection of Two Prevalent Mutations in West Algerian Population: A Rapid Genotyping Tool for the Frequent XPC Mutation c.1643_1644delTG.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder. Considering that XP patients have a defect of the nucleotide excision repair (NER) pathway which enables them to repair DNA damage caused by UV light, they have an increased risk of developing skin and eyes cancers. In the present study, we investigated the involvement of the prevalent XPA and XPC genes mutations-nonsense mutation (c.682C>T, p.Arg228X) and a two-base-pair (2 bp) deletion (c.1643_1644delTG or p.Val548Ala fsX25), respectively-in 19 index cases from 19 unrelated families in the West of Algeria. For the genetic diagnosis of XPA gene, we proceeded to PCR-RFLP. For the XPC gene, we validated a routine analysis which includes a specific amplification of a short region surrounding the 2 bp deletion using a fluorescent primer and fragment sizing (GeneScan size) on a sequencing gel. Among the 19 index cases, there were 17 homozygous patients for the 2 bp deletion in the XPC gene and 2 homozygous patients carrying the nonsense XPA mutation. Finally, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. The use of fragment sizing is the simplest method to analyze this 2 bp deletion for the DNA samples coming from countries where the mutation c.1643_1644delTG of XPC gene is prevalent.

[Molecular study of retinoblastoma in the Algerian population. Screening of Rb gene in constitutional and tumoral level]. / Étude moléculaire du rétinoblastome dans la population algérienne. Recherche de mutations du gène Rb au niveau constitutionnel et tumoral.

Inactivation of both alleles of the RB1 gene during normal retinal development initiates the formation of a retinoblastoma (RB) tumor. RB1 screening remains difficult, most of the alterations being unique and randomly distributed throughout the entire coding sequence. In this report, we present the results of a constitutionnal and tumoral RB1 analysis in Algerian population. The detection of RB1 gene deletion or mutation was performed by high performance liquid chromatography (HPLC) and sequence analyses in 21 patients. Germline abnormalities were found in 2/21 patients of sporadic unilateral retinoblastoma. The spectrum of germline and tumoral alterations included: three nonsense mutations; one mutation affecting splice site; one deletion and two polymorphisms. In general, for the 21 patients with no family history of the disease, we have identified mutations in germinal level in two of them showing that it is a transmissible form of retinoblastoma in these two cases known to be sporadic. A total of two mutations have not been previously reported.