ABCMdb

PMID: 7683952

Audrezet MP, Mercier B, Guillermit H, Quere I, Verlingue C, Rault G, Ferec C
Identification of 12 novel mutations in the CFTR gene.
Hum Mol Genet. 1993 Jan;2(1):51-4., [PubMed]

Sentences

No. Mutations Sentence Comment

37 ABCC7 p.Arg347Leu R347L This missense mutation changes an arginine (an amino acid with a basic side chain) for a leucine bearing a non-polar side chain. Login to comment 39 ABCC7 p.Arg347Leu The affected girl, a two year old compound heterozygote (genotype AF508/R347L), was diagnosed by systematic neonatal screening and up to now presented with no clinical symptoms (pancreatic sufficient). Login to comment 40 ABCC7 p.Arg347Pro ABCC7 p.Arg347His It appears that codon 347 could be a hot spot for mutations since two other nucleotide changes have been reported at nucleotide 1172 leading to R347P (12) or R347H which is associated with pancreatic sufficiency (Devoto, personal comm.). Login to comment 41 ABCC7 p.Ala349Val A349V This missense mutation results in a valine instead of an alanine due to a modification of nucleotide 1178 (C - T). Login to comment 47 ABCC7 p.Ala554Glu A554E The nucleotide at position 1733 was changed from a C to T leading to a glutamic acid for an alanine. Login to comment 51 ABCC7 p.Lys716* K716X Two nucleotide changes were detected in exon 13 of one CF chromosome. The nucleotide at position 2277 was changed from a A to G leading to a polymorphism Q715Q. Login to comment 58 ABCC7 p.Arg553* 3601-17 T - C This nucleotide change was detected in an affected child who carries an R553X mutation on the other chromosome. The nucleotide change is not situated in the 3' splice consensus sequence of intron 18 but as this change has never been observed on more than 200 normal alleles we have screened, one could expect that this mutation could affect splicing. Login to comment 60 ABCC7 p.Gln1238* Q1238X This C - T change, at position 3844, leads to a stop codon (TAG). Login to comment 62 ABCC7 p.Gly542* ABCC7 p.Gln1238* His genotype was G542X/Q1238X. Login to comment 67 ABCC7 p.Arg1162* 3898 insC The inserted base occurs at position 3898 and this frameshift mutation was detected in a severely affected, 20 year-old patient (pancreatic insufficient), bearing a nonsense mutation, R1162X, on the other chromosome. The mutation, which destroys an Alu I restriction site could be detected by failure of Alu I to digest the amplified PCR product. Login to comment 68 ABCC7 p.Trp57* W57X In exon 3 the nucleotide change at position 302 (G - A) leads to a change at codon 57 (TGG) encoding a tryptophan is changed to a TGA stop codon. Login to comment 70 ABCC7 p.Gln1313* Q1313X In exon 21, the nucleotide change at position 4069 (C - T) leads to a stop codon. Login to comment 79 ABCC7 p.Ala349Val ABCC7 p.Gln1238* ABCC7 p.Ala534Glu Lane 1: 3850-1 G-A, Lane 2: Q1238X, Lane 3: 2622 + 1 G-A, Lane 4: A349V, Lane 5: A534E. recently by DGGE resulting in high mutation detection rates, such as 95% in the factor Vm gene (25) or over 98% in the CFTR gene of the Breton population in the Celtic part of Brittany. Login to comment 91 ABCC7 p.Gln1238* ABCC7 p.Lys716* ABCC7 p.Trp57* ABCC7 p.Gln1313* The 3898 ins C in exon 20 is a frameshift mutation; the W57X, K716X, Q1238X and Q1313X are nonsense mutations. Login to comment 92 ABCC7 p.Arg347Leu ABCC7 p.Ala349Val ABCC7 p.Ala534Glu For the four other mutations: R347L and A349V in exon 7, A534E in exon 11 and 3601 -17 T - C, we have only indirect evidence in support of their being causative of disease: (i) these changes have never been observed on more than 300 non CF chromosomes so far examined (this panel of non CF chromosomes has been established from a series of non CF chromosomes, the normal alleles being deduced from non carrier siblings of non affected children); (ii) the missense mutations result in a switch to an amino acid of different polarity at that site; and (iii) the amino acids 347 (arginine) and 534 (alanine) are conserved in the CFTR of human, cow, Xenopus, mouse and dogfish, and the amino acid 349 (alanine) is conserved in the CFTR of human, cow and Xenopus (20). Login to comment 98 ABCC7 p.Arg347Leu ABCC7 p.Gly91Arg This notion has also been confirmed by a series of observations of the effects of missense mutations, such as Rl 17H (28), G91R (29) or R347L (this report), which are associated with pancreatic insufficiency and a milder form of the disease. Login to comment