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

Abstract

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.

Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins

“…Soufir et al [ 33 ] estimated the common ancestry to have occurred 1250–1500 years ago; this dates with the Saracens’ i.e., Arab-Muslims’ conquest of South Europe. Given reports of the same mutation in patients from Italian, Spanish, Egyptian, Algerian, and Libyan ancestries, c.1643_1644delTG was suggested to be a founder mutation for the Mediterranean region [ 43 , 46 ]. Nonetheless, c.1643_1644delTG mutation was also reported in Sudanese and German patients of Arabian ancestries.…”

The Role of Nitric Oxide in Cancer: Master Regulator or NOt?

“…Both GG-NER and TC-NER involve the basic mechanism: (1) recognition of the damaged sites (in transcribed and non-transcribed regions of the genome, respectively); (2) verification of DNA damage; (3) excision of damaged oligomers; and (4) gap filling by ligating intact molecules [ 90 ]. Defects in the NER pathway causes rare autosomal recessive diseases such as Xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD) [ 98 , 99 , 100 ]. NO was shown to inhibit DNA-adduct NER in human fibroblasts, including UVC and cisplatin derived DNA adducts [ 101 ].…”

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

“…Since, we started studying XP we reported five complementation groups (XP-A, C, D, E, and V) in Tunisia. The mutations with founder effect responsible for the XP-C (Ben Rekaya et al, 2009) and XP-A phenotypes (Messaoud et al, 2010) have been also found in other North African countries (Soufir et al, 2010) such as Morocco (Senhaji et al, 2013; Kindil et al, 2017), Egypt (Amr et al, 2014), Algeria (Bensenouci et al, 2016), and Libya (unpublished data). The XP-D and XP-E forms have been recently identified thanks to whole exome sequencing (WES) technology (Ben Rekaya et al, 2018).…”