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Two New XPD Patients Compound Heterozygous for the Same Mutation Demonstrate Diverse Clinical Features
journal contributionposted on 2023-06-07, 13:53 authored by Mitsuo Fujimoto, Suzanne N. Leech, Therina Theron, Masato Mori, Heather Fawcett, Elena Botta, Yasuyuki Nozaki, Takanori Yamagata, Shin-Ichi Moriwaki, Miria Stefanini, Mariko Y. Momoi, Hidemi Nakagawa, Sam Shuster, Celia Moss, Alan LehmannAlan Lehmann
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are both rare autosomal recessive disorders with defects in DNA repair. They are usually distinct both clinically and genetically but in rare cases, patients exhibit the clinical characteristics of both diseases concurrently. We report two new phenotypically distinct cases of XP with additional features of CS (xeroderma pigmentosum and Cockayne syndrome crossover syndrome (XP/CS)) carrying an identical mutation (G47R) in the XPD gene within the N terminus of the protein. Both patients had clinical features of XP and CS but only one fulfilled most criteria for diagnosing CS. Unusually, patient 1 developed early skin cancer, in contrast to patient 2, who never developed any malignancies. Cells from both these patients have repair defects typical of xeroderma pigmentosum complementation group D (XPD) cells, but also had the phenotype of uncontrolled DNA breakage found specifically in XPD/CS cells and similarly reduced levels of TFIIH. Despite these similarities between our two patients, their clinical features are quite different and the clinical severity correlates with other cellular responses to ultraviolet irradiation.
JournalJournal of Investigative Dermatology
PublisherNature Publishing Group
Notes0022-202x Journal Article GDSC142
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