A novel nonsense mutation identified in the first nucleotide binding fold of the CFTR gene in a Greek patient

• Published in: Human molecular genetics 1994-10, Vol.3 (10), p.1887-1888
• Main Authors: Balassopoulou, Angeliki, Papadakis, Manos, Loukopoulos, Dimitris
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Chloride Channels - genetics; cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator; Exons; Gastroenterology. Liver. Pancreas. Abdomen; Greece; Humans; Infant; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; man; Medical sciences; Membrane Proteins - genetics; Molecular Sequence Data; Other diseases. Semiology; Point Mutation; Polymorphism, Genetic; transmembrane conductance regulator
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/3.10.1887

Cystic Fibrosis (CF) is the most common autosomal recessive genetic disorder among the Caucasian population, affecting approximately 1 in 2000 neonates. This is true also for Greece where the frequency of carriers is estimated to be 1 in 25 to 30. Since the cloning of the CFTR gene in 1989, more than 450 disease causing mutations have been identified. These mutations include substitutions, deletions and insertions. While some of them have been reported in low frequencies, most of them represent unique cases. The distribution of the most common CFTR defects varies considerably among geographic and ethnic groups. Delta F508, a deletion of 3 base pairs that causes the loss of a phenylalanine residue at position 508 of the predicted protein accounts for 70% of the CF chromosomes in Northern Europe; this number is lower (of the order of 50%) in Southern Europe (4) (53% in Greece). In a previous study we have reported that 6 mutations (including Delta F508) characterize 70% of the Greek CF chromosomes. Identification of the underlying molecular defects in the remaining CF chromosomes is a major goal in this Laboratory. To this effect, our method of choice is the DGGE technique in which the detection of mutants through the abnormal patterns they produce on electrophoresis is followed by direct sequencing of the PCR product. As a result of these studies, we report here a novel nonsense mutation in exon 10 of the CFTR gene which was recently identified in trans with another as yet uncharacterised CF mutation in a Greek patient with typical severe CF.