Two new XPD patients compound heterozygous for the same mutation demonstrate diverse clinical features.
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.
Fujimoto
Mitsuo
M
Department of Dermatology, Jichi Medical School, Japan.
Leech
Suzanne N
SN
Theron
Therina
T
Mori
Masato
M
Fawcett
Heather
H
Botta
Elena
E
Nozaki
Yasuyuki
Y
Yamagata
Takanori
T
Moriwaki
Shin-Ichi
S
Stefanini
Miria
M
Momoi
Mariko Y
MY
Nakagawa
Hidemi
H
Shuster
Sam
S
Moss
Celia
C
Lehmann
Alan R
AR
D000328:Adult; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D004260:DNA Repair; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012878:Skin Neoplasms / Q000209:etiology*; D019473:Transcription Factors, TFII / Q000097:blood; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000175:diagnosis / Q000473:pathology
D019473:Transcription Factors, TFII