Molecular and cellular analysis of the DNA repair defect in a patient in Xeroderma pigmentosum complementation group D who has the clinical features of Xeroderma pigmentosum and Cockayne syndrome

Journal Article · Sun Jan 01 00:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:70379

Broughton, B C; Thompson, A F; Harcourt, S A; Cole, J; Arlett, C F; Lehmann, A R ^[1]; Vermeulen, W; Hoeijmakers, J H.J. ^[2]; Botta, E; Stefanini, M ^[3]

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1. Univ. of Sussex, Brighton (United Kingdom)
2. Erasmus Univ., Rotterdam (United Kingdom)
3. Istituto di Genetica, Pavia (Italy); and others

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level of nucleotide excision repair that is 30%-40% that of normal cells. The deficiency is assigned to the XP-D complementation group, and we have identified two causative mutations in the XPD gene: a gly{yields}arg change at amino acid 675 in the allele inherited from the patient`s mother and a -1 frameshift at amino acid 669 in the allele inherited from his father. These mutations are in the C-terminal 20% of the 760-amino-acid XPD protein, in a region where we have recently identified several mutations in patients with trichothiodystrophy. 44 refs., 5 figs., 2 tabs.

• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 70379
• Journal Information: American Journal of Human Genetics, Vol. 56, Issue 1; Other Information: PBD: Jan 1995
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
HUMAN CHROMOSOMES
GENE MUTATIONS
PATIENTS
XERODERMA PIGMENTOSUM
MENTAL DISORDERS
SKELETAL DISEASES
GENES
AMINO ACID SEQUENCE
DNA REPAIR
DEFECTS
DNA
BIOLOGICAL RADIATION EFFECTS
ULTRAVIOLET RADIATION
FIBROBLASTS
POLYMERASE CHAIN REACTION