Xeroderma pigmentosum: Diagnostic procedures, interdisciplinary patient care, and novel therapeutic approaches

Abstract

SummaryXeroderma pigmentosum (XP) is an autosomal recessive disease, caused by a gene defect in the nucleotide-excision-repair (NER) pathway or in translesional DNA synthesis. At the age of eight, patients already develop their first skin cancers due to this DNA repair defect. In contrast, in the Caucasian population the first tumor formation in UV exposed skin regions occurs at a mean age of 60. The clinical picture among patients suffering from XP is highly diverse and includes signs of accelerated skin aging, and UV-induced skin cancers, as well as ophthalmologic and neurological symptoms. Patients should therefore receive interdisciplinary care. This includes dermatologists, ophthalmologists, ENT specialists, neurologists, and human geneticists. Patients with XP are clinically diagnosed, but this may be supported by molecular-genetic and functional analyses. These analyses allow pinpointing the exact disease-causing gene defect (complementation group assignment, detection of the type and location of the mutation within the gene). The resulting information is already relevant to predict the course of disease and symptoms and probably will be utilized for individualized therapeutic approaches in the future. Recently, enhanced repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons by certain antibiotics could be demonstrated.

Photosensitive form of trichothiodystrophy associated with a novel mutation in the XPD gene

“…As TTD comprises a rare autosomal recessive, extremely heterogeneous, multisystem disorder characterized by sulfur-deficient brittle hair, mental and growth retardation, nail abnormalities, ichthyosis, ocular and skeletal abnormalities, and recurrent infections (4,(6)(7)(8), our case highlights the necessity of regular interdisciplinary follow-up examinations to identify orphan diseases and guide families. The xeroderma pigmentosum (XP) group D gene is a subunit of the DNA repair/transcription factor TFIIH.…”

Passenger Hotspot Mutations in Cancer

“…We identify an N238S mutation recurrent in 9 bladder patients. Germline SNPs in ERCC2 are associated with xeroderma pigmentosum, which greatly elevates cancer risk (Lehmann et al, 2014). However, ERCC2's status as a somatic driver had not been characterized until recently (Kim et al, 2016).…”

Molekulare Mechanismen der kutanen Photokarzinogenese: ein Update

“…Defekte dieses Reparaturweges verursachen die seltene autosomal-rezessive Erkrankung Xeroderma pigmentosum (XP). Eine umfassende Zusammenfassung finden Sie in [7] sowie in dem Artikel "Xeroderma pigmentosum -Fakten und Perspektiven" (siehe S. 232 -236 in diesem Heft).…”