ABSTRACT
XP is a sun-sensitive and cancer-prone genetic disorder, consisting of eight (group A-G) genetically distinct complementation groups. Some XP group D patients exhibit clinical symptoms of other genetic disorders, CS, and TTD. The XP group D gene (XPD gene) product is required for nucleotide excision repair and is one of the components of basal transcription factor TFIIH as well. Therefore, different mutations in the XPD gene may result in a variety of clinical manifestations. Here we report on two causative mutations of the XPD gene in XP61OS, a Japanese XP group D patient who has only mild skin symptoms of XP without CS, TTD, or other neurological complications. One of the mutations was the 4-bp deletion at nucleotides 668-671, resulting in frameshift and truncation of the protein. The other was a nucleotide substitution leading to Ser-541 to Arg (S541R) in helicase domain IV of the XPD protein. The patient's father was heterozygous for the 4-bp deletion, while the mother was heterozygous for the S541R mutation. Thus, the parents were obligate carriers of the XP-D trait. The expression study showed that the XPD cDNA containing the deletion or the S541R missense mutation failed to restore the UV sensitivity of XP6BE, group DaXP cells, while the wild-type XPD cDNA restored it to the normal level. However, the transfectant expressing the XPD cDNA with the missense mutation was slightly more resistant than the parental XP6BE cells. These findings are consistent with the mild symptoms of the XP61OS patient.
Subject(s)
DNA Helicases , DNA-Binding Proteins , Point Mutation/genetics , Proteins/genetics , Sequence Deletion/genetics , Transcription Factors , Xeroderma Pigmentosum/genetics , Cells, Cultured , DNA Mutational Analysis , DNA, Complementary/genetics , Fibroblasts/radiation effects , Gene Expression Regulation , Genetic Complementation Test , Humans , Infant , Japan , Male , Microinjections , Polymorphism, Restriction Fragment Length , RNA, Messenger/analysis , Skin/pathology , Ultraviolet Rays , Xeroderma Pigmentosum/pathology , Xeroderma Pigmentosum Group D ProteinABSTRACT
We have devised a new in vitro model of type I cutaneous anaphylaxis. Male albino rats were sensitized with DNP-Ascaris. Abdominal skin was shaved, and thin, split-thickness slices of skin were cut with a dermatome. The dermis was excised and cut into 100 mg pieces. The dermal tissue was incubated with antigen in Tyrode's solution for 30 min at 37 degrees C. Antigen-induced histamine release from dermal tissue was measured fluorimetrically. Using this system, we measured histamine release from PUVA-irradiated and non-irradiated dermal tissues. A single PUVA irradiation inhibited type I cutaneous anaphylaxis, but did not affect spontaneous histamine release or total dermal histamine. Our model is considered to be useful for investigation of the mechanism of suppression of type I cutaneous anaphylaxis by PUVA.
Subject(s)
Anaphylaxis/metabolism , Histamine Release/radiation effects , PUVA Therapy , Skin/metabolism , Anaphylaxis/etiology , Animals , Histamine Release/drug effects , In Vitro Techniques , Male , Passive Cutaneous Anaphylaxis/drug effects , Passive Cutaneous Anaphylaxis/radiation effects , Rats , Rats, Inbred StrainsABSTRACT
A case of generalized granuloma annulare associated with temporal arteritis is described. The patient, a 79-year-old man, noticed numerous asymptomatic lesions on his trunk and extremities for 3 months. Four months later, he suffered from headache and loss of vision. Both were successfully treated by oral administration of prednisolone.
