Founder mutations in xeroderma pigmentosum

Abstract

In this issue, Soufir et al. report a founder mutation in the XPC DNA repair gene in 74% of families with xeroderma pigmentosum (XP) in the Maghreb region (Algeria, Morocco, and Tunisia) of northern Africa. These patients have a high frequency of skin cancer. The presence of this founder mutation provides an opportunity for genetic counseling and early diagnosis of XP.

Figure 1. Haplotype analysis distinguishes a mutation hotspot from a founder mutation

(a) Mutation hotspot. (Top row) The same mutation (delTG) arises independently in two individuals with different single-nucleotide polymorphism (SNP) haplotypes in the region of the mutation: TA (delTG) G (solid rectangle) and CG (delTG) G (dotted rectangle). Over generations these individuals pass the delTG mutation and adjacent regions to their progeny, who are asymptomatic carriers with one mutated allele and one normal allele (center row). Eventually, carriers of the delTG mutation have children with the same mutation in both alleles (bottom row). All of these affected individuals (XP patients) are homozygous for the delTG mutation. However, different XP patients have different haplotypes (TA (delTG) G, CG (delTG) G, or both). (b) Founder mutation. (Top row) The delTG mutation arises in one individual with a SNP haplotype in the region of the mutation: CA (delTG) T (dashed rectangle). This individual passes the delTG mutation and adjacent regions to many generations of progeny who are asymptomatic carriers with one mutated allele and one normal allele (center row). Eventually, two carriers of the delTG mutation have a child with the same mutation in both alleles (bottom row). All of the affected individuals are homozygous for the delTG mutation and have the same haplotype (CA (delTG) T).