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Diagnosis of Xeroderma pigmentosum variant in a young patient with two novel mutations in the POLH gene
Author(s) -
De Palma Armando,
Morren MarieAnne,
Ged Cécile,
Pouvelle Caroline,
Taïeb Alain,
Aoufouchi Said,
Sarasin Alain
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38340
Subject(s) - xeroderma pigmentosum , somatic hypermutation , microbiology and biotechnology , mutation , exon , polymerase , gene , biology , dna polymerase , genetics , nucleotide excision repair , dna repair , cancer research , antibody , b cell
We describe the characterization of Xeroderma Pigmentosum variant (XPV) in a young Caucasian patient with phototype I, who exhibited a high sensitivity to sunburn and multiple cutaneous tumors at the age of 15 years. Two novel mutations in the POLH gene, which encodes the translesion DNA polymerase η, with loss of function due to two independent exon skippings, are reported to be associated as a compound heterozygous state in the patient. Western blot analysis performed on proteins from dermal fibroblasts derived from the patient and analysis of the mutation spectrum on immunoglobulin genes produced during the somatic hypermutation process in his memory B cells, show the total absence of translesion polymerase η activity in the patient. The total lack of Polη activity, necessary to bypass in an error‐free manner UVR‐induced pyrimidine dimers following sun exposure, explains the early unusual clinical appearance of this patient.