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

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

To explore the manifestations of XP variants in patients from Türkiye.

Our multicentric investigation involved 69 patients with XP from 52 unrelated families across 12 centres in Türkiye. Clinical examinations and genetic tests were conducted to assess the correlation between variants and disease characteristics.

Of the XP groups, XP-C was the most prevalent (n = 38; 55%), followed by XP-variant (n = 15; 22%), XP-E (n = 8; 12%), XP-D (n = 4; 6%), XP-A (n = 3; 4%) and XP-G (n = 1; 1%). XP-B and XP-F were not identified. Median patient age at diagnosis was 9 years (interquartile range 2-19), although this varied significantly according to complementation group, with XP-D and XP-V diagnoses occurring later. Genetic analyses revealed 30 novel variants, including one in a patient with XP/Cockayne syndrome complex. Despite the link of XP-D to neurological degeneration, none of the patients showed neuropathy, while three patients with XP-E had neurological involvement. Notably, 26% (n = 18) of patients reported no consanguinity, yet a significant proportion (n = 11/18) had distant family members with XP.

We found unique clinical patterns and diversity among complementation groups in Turkish patients with XP. Future investigations should focus on functional characterization of the novel variants, preferably through assays like unscheduled DNA synthesis, to determine their potential impact on DNA repair mechanisms and their implications for improved patient care.