ABCMdb

PMID: 7512860

Savov A, Mercier B, Kalaydjieva L, Ferec C
Identification of six novel mutations in the CFTR gene of patients from Bulgaria by screening the twenty seven exons and exon/intron boundaries using DGGE and direct DNA sequencing.
Hum Mol Genet. 1994 Jan;3(1):57-60., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Gly1069Arg ABCC7 p.Gln493Arg In this case the possible pathogenic role of G1069R remains to be determined by the presence of this missense mutation as the only alteration in a CF allele (figure 1) Q493R An A-G transition at position 1610 in exon 10 was found in a single CF allele of Turkish origin. Login to comment 11 ABCC7 p.Tyr919Cys Clinical symptoms include pancreatic insufficiency, severe lung involvement with St aureus colonization, frequent pulmonary infections, chronic dyspnea and respiratory insufficiency (figure 1) Y919C An A-G substitution at position 2888 in exon IS was detected in a Gypsy CF allele in which haplotype characterization was not possible. Login to comment 12 ABCC7 p.Tyr919Cys The mutation results in the substitution of cysteine for tyrosine at position 919 of the CFTR protein. Login to comment 13 ABCC7 p.Tyr919Cys The nature of the amino acid replacement and the lack of other nucleotide variations in this patient's DNA suggest that Y919C is a disease causing mutation. Login to comment 22 ABCC7 p.Arg347Pro ABCC7 p.Gly542* ABCC7 p.Arg1070Gln Preliminary studies on the molecular basis of CF in Bulgaria have shown that AF5O8 accounts for about 55% of the mutant alleles (9) with the N13O3K accounting for 6% (10), the G542X for 5% and three additional mutations including 1677 del TA, R1070Q and R347P for about 8%. Login to comment 39 ABCC7 p.Leu88* This has permitted us to identify the following previously undescribed alleles: L88X A T - G transversion at nucleotide position 395 in exon 3 was detected in one Bulgarian CF allele of haplotype 2/1/1/16/28/13. Login to comment 42 ABCC7 p.Gly1069Arg A second nucleotide variation, G1069R (see below) was identified in the same (maternal) chromosome. Login to comment 45 ABCC7 p.Gly1069Arg Symptoms include pancreatic insufficiency and severe lung involvement with emphysema and chronic respiratory insufficiency (figure 1) G1069R The nucleotide substitution G-A at position 3337 in exon 17b was found in the same CF allele which carries the nonsense mutation in codon 88. Login to comment 59 ABCC7 p.Leu88* Among the 6 molecular defects reported in this work, two are clearly defective alleles (L88X and Q2X), as these nucleotide changes lead to a stop codon. Login to comment 62 ABCC7 p.Gln493Arg ABCC7 p.Tyr919Cys It is obvious that other experiments as RNA analysis in order to objective its effect on splicing are necessary to definitively prove that the 1717-8 G-A is a defective allele. The missense mutations Y919C and Q493R are drastic amino acid changes at the protein level and moreover on these two chromosomes no other change was observed through a complete screening, this renders very probable that these missense mutations correspond to a CFTR allele. The analysis of CF alleles has resulted in the identification of six novel mutations, all occurring in single mutant chromosomes. Login to comment 68 ABCC7 p.Gly1069Arg Additional examples of G1069R, if detected, will help to evaluate its effect on the CFTR protein. Login to comment 74 ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg1070Gln The most common mutations of the CFTR gene (AF508, N1303K, G542X, 1677 del TA, R347P, R1070Q) have been in a first step identified and in our ongoing effort to identify the other mutations, we have fully scanned the entire coding sequence of 35 CF patients. Login to comment