ClinVar

For discussion of the arg788-to-trp (R788W) mutation in the ERCC4 gene that was found in compound heterozygous state in a patient with xeroderma pigmentosum type F (XPF; 278760) by Sijbers et al. (1996), see 133520.0001.

Sijbers et al. (1998) found the R788W mutation in homozygous state in a second Caucasian patient with XPF. Mild ocular photophobia had been present from childhood, and acute skin reactions occurred upon exposure to sunlight. Basal and squamous cell carcinomas developed after his twenty-seventh year. In his late forties, progressive neurologic symptoms emerged, which included intellectual decline, mild chorea and ataxia, and marked cerebral and cerebellar atrophy. Sijbers et al. (1998) stated that such neurologic abnormalities were unusual in XPF, having been described in only 1 of 17 other XPF individuals. The patient's 5-fold reduced activity of nucleotide excision repair in cultured cells, combined with moderately affected cell survival and DNA replication after UV exposure, was typical of XPF. Biochemical, genetic, and clinical data indicated the presence of considerable residual repair activity, strongly suggesting that the R788W mutation is leaky. The 2 Caucasian patients carrying this mutation were not known to be related.