Molecular analysis of neurofibromatosis type 1 mutations

✍ Scribed by Xu Weiming; Qi Yu; Liu Lizhi; Margaret Ponder; Margaret Wallace; Xu Gangfeng; Bruce Ponder

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 377 KB
• Volume: 1
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380010604

✦ Synopsis

Communicated by Robert Williamson

We have examined a panel of 115 unrelated N F l individuals for mutation in the 3' region of the N F l gene, using Southern blotting and polymerase chain reaction amplification of exons followed by singlestrand conformation polymorphism (SSCP) analysis. We found only 2 unequivocal mutations: a 5 7 1 bp deletion which removed exon 6 and resulted in a frameshift in exon 7, and a 2 bp deletion in exon 1. A third sequence variation detected by SSCP was predicted to cause a lysine-arginine substitution in exon 6. This is a conservative change, and since the affected individual is a new mutation whose parents are not available, we cannot be sure of its biological significance. We detected mutations in at most 3% of individuals, from an analysis which covered 17% of the coding sequence by SSCP and a larger region by Southern blotting. This relative failure to detect mutations accords with the experience of others. Even allowing for the incomplete sensitivity of the methods used, the results suggest that the majority of NF1 mutations lie elsewhere in the coding sequence or outside it.