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xeroderma pigmentosum, complementation group D (XPD)

Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-D patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.

Linkage of trichothiodystrophy (TTD) and xeroderma pigmentosum of complementation group D was suggested by Nuzzo et al. (1986) on the basis of 3 Italian families in which 4 persons had the 2 disorders. Study of surnames and genealogies suggested that the 3 sibships probably had a common ancestral couple. The characteristics of the TTD were hair shaft abnormalities, ichthyosis, immature sexual development, short stature, and peculiar facies. It may be the disorder called Tay syndrome (see 601675). The form in the same complementation group as XPD might be referred to as TTD1; the second type (TTD2) is also described in 601675.
Johnson and Squires (1992) stated that more than 30 unrelated persons with XP of group D were known and that less than half of this number showed major abnormalities of the CNS, once considered to be the hallmark of XPD. They also commented on the fact that some patients with trichothiodystrophy or with Cockayne syndrome have mutations in the XPD gene. Stefanini et al. (1986) pointed out that the only known patient with complementation group B xeroderma pigmentosum (610651) had clinical features of Cockayne syndrome (216400) and, further, that the only known patient thought to have complementation group H xeroderma pigmentosum also had Cockayne syndrome. Stefanini et al. (1986) reported studies on the defect in DNA repair with creation of heterokaryons. Seetharam et al. (1987) used a shuttle vector plasmid to assess the types of mutations that cells from a patient with xeroderma pigmentosum of complementation group D introduce into UV-damaged, replicating DNA. In comparison to UV-treated plasmids replicated in normal cells, there were fewer surviving plasmids, a higher frequency of plasmids with mutations, fewer plasmids with 2 or more mutations in the marker gene (coding for a tyrosine suppressor transfer RNA), and a new mutagenic hotspot. The major type of base substitution was the G:C to A:T transition. Similar findings were reported with cells from a xeroderma pigmentosum patient in complementation group A (278700). Ichihashi et al. (1988) described mild skin lesions and no apparent neurologic abnormalities at the age of 31 years despite the usual group D level of DNA repair deficiency and cultured fibroblasts in a case classified as complementation group D by cell-fusion complementation methods. Arrand et al. (1989) cloned and characterized a hamster DNA repair gene that is able to confer an increase in resistance to ultraviolet irradiation on 2 XPD cell lines but not on an XPA line. They found no obvious similarities to 2 human excision repair genes, ERCC1 (126380) and ERCC2, which correct repair-defective hamster cells but have no effect on XP cells. (Flejter et al. (1992) found that ERCC2 did correct the defect in XPD cells.) Homologs of the hamster gene were identified in normal human genomic DNA and mRNA. The transcription pattern was not altered in XPD or XPA cells. The gene complementing group D xeroderma pigmentosum has been cloned (Takebe, 1989).



TYPE: sensitivity to radiation

Related patway(s): nucleotide excision repair (NER), transcription factors

DNAtraffic protein(s) related to disease: ERCC2 (XPD)

OMIM: 278730

Last modification date: Aug. 17, 2011