CASE REPORT   

Giornale Italiano di Dermatologia e Venereologia 2020 June;155(3):349-54

DOI: 10.23736/S0392-0488.16.05158-0

Copyright © 2016 EDIZIONI MINERVA MEDICA

lingua: Inglese

Rare exon 10 deletion in POLH gene in a family with xeroderma pigmentosum variant correlating with protein expression by immunohistochemistry

Riccardo G. BORRONI ¹ ✉, Marta DIEGOLI ², Maurizia GRASSO ¹, Monica CONCARDI ¹, Manuela AGOZZINO ¹, Mariadelaide VIGNINI ^{3, 4}, Eloisa ARBUSTINI ¹

¹ Laboratories of Experimental Research in Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; ² Department of Molecular Medicine, University of Pavia, Pavia, Italy; ³ Division of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; ⁴ Division of Dermatology, Department of Surgical, Diagnostics, and Pediatric Sciences, University of Pavia, Pavia, Italy

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by severe cutaneous and ocular sensitivity to sunlight, leading to skin cancer. Most XP patients belong to the XP complementation groups (XP-A to XP-G), due to mutations in genes involved in nucleotide excision repair (NER). On the other hand, the XP Variant type (XP-V, OMIM#278750), which accounts for about 20% of all XP patients, is associated with normal NER function. The disease gene is POLH, which encodes polymerase η (pol η) allowing translesion synthesis in regions of DNA damage. We observed an Italian family presenting with photosensitivity, freckling since childhood and multiple skin cancers. Complete sequence analysis of XPA, XPC, XPD/ERCC2 genes and exons 1-9 and 11 of POLH gene did not reveal pathological mutations. No PCR product was observed for exon 10 in POLH gene. By RT-PCR analysis followed by POLH exon 10 sequencing, all affected members were found to harbor a homozygous 170-nucleotide deletion. The same deletion was previously described in 3 XP-V families, one of southern Italian descent and two from Algeria, suggesting a possible founder mutation. The deletion determines a severe protein truncation and defective pol η activity. Immunohistochemical study showed markedly reduced pol η expression in skin lesions of the affected siblings compared to the normal control skin.

KEY WORDS: Xeroderma pigmentosum; DNA-directed DNA polymerase; Rad30 protein; Sequence deletion; Mutation; Immunohistochemistry