A new mutation in the CFTR gene, composed of two adjacent DNA alterations, is a common cause of cystic fibrosis among Georgian Jews

Journal Article · Fri Jan 01 04:00:00 EST 1993 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1993.1046· OSTI ID:6707089

Shoshani, T; Berkun, Y; Yahav, Y; Augarten, A; Bashan, N; Rivlin, Y; Gazit, E; Sereth, H; Kerem, E; Kerem, B S ^[1]

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1. Hebrew Univ., Jerusalem (Israel)

Five Jewish cystic fibrosis (CF) patients from four unrelated families, all of whom emigrated from what was Soviet Georgia were studied. The parents in two of the families are first-degree relatives. The clinical phenotype of the patients seems to be associated with a severe disease, as reflected by early age of diagnosis (before the age of 1 year), high sweat chloride level (105-140 meq/liter), and pancreatic insufficiency. The pulmonary function and nutritional status of these patients are normal. These patients were tested for [Delta]F508 by analysis of heteroduplex DNA (4). None of the CF chromosomes was found to carry the [Delta]F508 mutation. Subsequently, PCR-amplified genomic DNA samples from two of these patients were subjected to direct sequencing (5) of regions containing exons 7, 9-12, an 19-21 of the CF gene using the oligonucleotides previously described (3, 6). In exon 7, two DNA alterations 3 bp apart were identified in both patients. The first alteration in a C [yields] A transversion at nucleotide position 1207, changing the glutamine codon to lysine (Q359K). The second DNA alteration is a C [yields] A transversion at nucleotide position 1211 changing the threonine codon to lysine (T360K). The two DNA alterations cause nonconservative amino acid substitutions, changing each of the two uncharged polar amino acids (glutamine and threonine) to a basic amino acid, lysine. The Q359K substitution destroys an Rsal recognition site and can be detected by PCR amplification of exon 7 using 7i-5 and 7i-3 oligonucleotides (6), followed by Rsal digestion and electrophoresis on 10% polyacrylamide gels. Two Rsal sites are found in a normal amplified DNA fragment, resulting in three restriction fragments of 292, 68, and 50 bp. Digestion of the PCR fragment of an individual homozygous for this substitution resulted in only two fragments of 342 and 68 bp. 6 refs., 3 figs.

• OSTI ID: 6707089
• Journal Information: Genomics; (United States), Journal Name: Genomics; (United States) Vol. 15:1; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMIDES
AMINO ACIDS
AMPLIFICATION
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY FLUIDS
CARBOXYLIC ACIDS
CHROMOSOMES
COLLOIDS
DEVELOPED COUNTRIES
DIAGNOSIS
DIGESTION
DISPERSIONS
DNA
ELECTROPHORESIS
FIBROSIS
GELS
GENE MUTATIONS
GENES
GEORGIA
GLUTAMINE
HYDROXY ACIDS
LYSINE
MATERIALS
MUTATIONS
NORTH AMERICA
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOLOGICAL CHANGES
PATIENTS
PHENOTYPE
SWEAT
THREONINE
USA
WASTES