TY - JOUR
T1 - Diagnosis of Xeroderma pigmentosum variant in a young patient with two novel mutations in the POLH gene
AU - De Palma, Armando
AU - Morren, Marie Anne
AU - Ged, Cécile
AU - Pouvelle, Caroline
AU - Taïeb, Alain
AU - Aoufouchi, Said
AU - Sarasin, Alain
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - cutaneous tumor
KW - POLH gene
KW - sun sensitivity
KW - translesion polymerase
KW - xeroderma pigmentosum variant
UR - http://www.scopus.com/inward/record.url?scp=85022209367&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.38340
DO - 10.1002/ajmg.a.38340
M3 - Article
C2 - 28688171
AN - SCOPUS:85022209367
SN - 1552-4825
VL - 173
SP - 2511
EP - 2516
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -