Frameshift mutation at codon 642 of the hMLH1 gene in human endometrial cancer

✍ Scribed by Shinichi Fukushige; Shigeru Wakatsuki; Satoru Nagase; Akira Horii

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 212 KB
• Volume: 8
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380080404

✦ Synopsis

MUTATION NOTES

single-strand conformational polymorphism (SSCP) analysis, 22 exons and 196 bp of the 5' region of the PDEB gene were screened. Primers were derived from Riess et al. (1992). The samples corresponding to the two affected RP patients had an altered migration band in exon 13 compared with controls while the SSCP pattern in both parents suggested that they are heterozyguous carriers of the mutation. Sequence analysis was performed on the PCR product of exon 13 and a G-to-A transition in codon 552 was detected. This change results in the substitution of a hydrophilic arginine aminoacid by a neutral glutamine residue.

Rod photoreceptor cell cGMP-specific PDE is a key enzyme in phototransduction. Inactivation of PDE by mutations in PDEB would lead to accumulation of rod cGMP, and it has been suggested that this is deleterious for the photoreceptor cells (Lolley et al., 1977). The catalytic site of the cGMP hydrolysis has been assigned to the peptide region between residues 555-790 in the human protein. Therefore, the G-to-A change close to this catalytic core would involve a modification in the structural conformation of the protein that would disturb the physiological hydrolysis of cGMP.

Acknowledgements

Espafiol).