PROTEIN TRUNCATION TEST - ANALYSIS OF 2 NOVEL POINT MUTATIONS AT THE CARBOXY-TERMINUS OF THE HUMAN DYSTROPHIN GENE ASSOCIATED WITH MENTAL-RETARDATION

Approximately one-third of the mutations responsible for Duchenne musc ular dytrophy (DMD) do not involve gross rearrangements of the dystrop hin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-termin ating mutations. A number of data raised the possibility that the C-te rminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation anal ysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutat ions in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation te rmination of dystrophin. The possible effects on the reading frame wer e analyzed by the study of reverse transcripts amplified from peripher al blood lymphocytes mRNA and by the protein truncation test. (C) 1995 Wiley Liss, Inc.