Genotype-phenotype associations in a robust cohort of 69 xeroderma pigmentosum patients across Türkiye: a multicenter study

Abstract

Background: Xeroderma pigmentosum (XP) is a rare DNA damage repair disorder. Seven distinct complementation groups and XP-variant form have been identified; however, limited literature exists on the genotype-phenotype correlation in XP.

Objective: This study explores XP manifestations associated with variants in patients from Türkiye.

Methods: A multicentric investigation involved 69 XP patients from 52 unrelated families across 12 centers in Türkiye. Clinical examinations and genetic testing were conducted to assess the correlation between variants and disease characteristics.

Results: XP-C group was the most prevalent group (n=38, 55%), followed by XP-V (n=15, 21.7%), XP-E (n=8, 11.6%), XP-D (n=4, 5.8%), XP-A (n=3, 4.3%), and XP-G (n=1, 1.4%). No XP-B and XP-F groups were identified. The median diagnosis age was 8.5 years, though this varied significantly among complementation groups, with diagnoses in XP-D and XP-V occurring later. Genetic analyses revealed 30 novel variants, including one in a patient with XP/Cockayne syndrome complex. Despite XP-D's link to neurological degeneration, none showed neuropathy, while three XP-E patients exhibited neurological involvement. Notably, 26% (n=18) of patients reported no consanguinity, yet a significant proportion (11/18) had distant family members with XP.