A 32-bp deletion (2991del32) in the cystic fibrosis gene associated with CFTR mRNA reduction

✍ Scribed by Thilo Dörk; Katrin Will; Klaus Grade; Michael Krawczak; Burkhard Tümmler

• Book ID: 102860867
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 550 KB
• Volume: 4
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380040111

✦ Synopsis

Communicated by Lnp-Chee Tsui

Cystic fibrosis, a common recessive disorder of exocrine glands, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the identification of a 32-bp deletion within the coding region of CFTR that involves the nucleotides 2991-3022 in exon 15 (2991de132). This unusual frameshift mutation was confirmed in three unrelated German families, accounting for a frequency of 0.3% in 1,028 CF chromosomes. All identified patients are compound heterozygotes for 2991de132 and for the most frequent cystic fibrosis mutation, AF508. The evaluation of clinical data revealed typical symptoms of cystic fibrosis, including pancreatic insufficiency, in all three index cases. To characterize further the mutation in the CFTR transcript, we analysed RNA from lymphocytes by reverse transcription and PCR amplification. 2991de132 transcripts were detectable neither in the R N A sample from a patient compound heterozygous AF508/2991de132 nor in the parental sample heterozygous wild-type12991de132. These data indicate that the 32-bp deletion causes a pancreas insufficient cystic fibrosis phenotype by a severe reduction of CFTR mRNA.