ABCMdb

PMID: 7529962

Mercier B, Verlingue C, Lissens W, Silber SJ, Novelli G, Bonduelle M, Audrezet MP, Ferec C
Is congenital bilateral absence of vas deferens a primary form of cystic fibrosis? Analyses of the CFTR gene in 67 patients.
Am J Hum Genet. 1995 Jan;56(1):272-7., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Gly149Arg ABCC7 p.Arg258Gly ABCC7 p.Ala800Gly ABCC7 p.Glu193Lys We have identified four novel missense mutations (A800G, G149R, R258G, and E193K). Login to comment 24 ABCC7 p.Arg117His They also reported the frequent occurrence of a second mutation in theirgroup ofpatients, the mutation R117H (Gervais et al. 1993). Login to comment 63 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* We identified 28 AF508, 5 W1282X, 1 G542X, 1 R553X, and 2 N1303K mutations. Login to comment 65 ABCC7 p.Arg117His ABCC7 p.Arg347His ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Gly149Arg ABCC7 p.Arg258Gly ABCC7 p.Ser1235Arg ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Arg668Cys ABCC7 p.Arg117Cys ABCC7 p.Ala800Gly ABCC7 p.Arg1066His ABCC7 p.Glu193Lys ABCC7 p.Gly628Arg ABCC7 p.Arg75Leu In addition, we identified the following missense mutations: four R668C, one A800G, one (G628R + S1235R, borne on the same chromosome), one (R74W + D1270N, borne on the same chromosome), six R117H, one F1052V, one R117C, one S1235R, one G149R, one R258G, two R347H, one R1066H, one R75L, and one E193K. Login to comment 77 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Gly149Arg ABCC7 p.Arg258Gly ABCC7 p.Ser1235Arg ABCC7 p.Ser1235Arg ABCC7 p.Phe1052Val ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg668Cys ABCC7 p.Arg117Cys ABCC7 p.Ala800Gly ABCC7 p.Arg1066His ABCC7 p.Glu193Lys ABCC7 p.Gly628Arg ABCC7 p.Arg75Leu of Patients Genotypea 1 AF508 + (G628R + S1235R) 1 AF508 + (R74W + D1270N) 2 AF508 + R668C 4 AF508 + R117H 1 AF508 + R258G 1 AF508 + R75L 1 E193K + N1303K 1 R347H + R1066H 1 R117C + W1282X 1 R553X + R668C 1 G149R + R668C 1 R117H+R117H 18 AF508/unidentified 4 W1282X/unidentified 1 G542X/unidentified 1 N1303K/unidentified 1 S1235R/unidentified 1 R347H/unidentified 1 A800G/unidentified 1 F1052V/unidentified 23 unidentified/unidentified a In parentheses are the two mutations located on the same haplotype. Login to comment 84 ABCC7 p.Gly149Arg (ii) The second change, situated in exon 4, is G-o.A at position 577 and corresponds to the substitution of a glycine for an arginine (G149R). Login to comment 85 ABCC7 p.Gly628Arg ABCC7 p.Gly1061Arg It has been reported elsewhere that such an amino acid change could be considered as mild, as for G628R in exon 13 (Fanen et al. 1992) and G1061R in exon 17b (Mercier et al. Login to comment 87 ABCC7 p.Arg258Gly ABCC7 p.Arg258Gly (iii) The third novel mutation we found is R258G, and the nucleotide change is G-A at position 904 in exon 6b. It corresponds to the substitution of an arginine for a glycine (R258G) This mutation is situated in a region that encodes part of the transmembrane region of the protein, and the mutation results in a change of polarity at codon 258. Login to comment 88 ABCC7 p.Glu193Lys (iv) The fourth novel mutation we have observed occurs at position 709 and corresponds to a G--.A change that results in a glutamic acid codon instead of a lysine codon (E193K). Login to comment 92 ABCC7 p.Gly149Arg ABCC7 p.Arg258Gly ABCC7 p.Glu193Lys For all four of these new mutations, a segregation analysis was performed in each family, allowing us to show that G149R, R258G, and E193K were carried by a particular allele and that these mutations were not de novo mutations. Login to comment 98 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Two patients were carriers of two missense mutations on the same allele (G268R + S1235 R and R74W + D1270N) (table 1). Login to comment 99 ABCC7 p.Arg74Trp ABCC7 p.Ser1235Arg The association of these two missense mutations on the same haplotype is interesting, as both S1235R and R74W have been independently reported elsewhere to be CFTR alleles (Claustres et al. 1993; Cuppens et al. 1993). Login to comment 100 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp We also had previously reported that haplotype R74W + D1270N was present in a healthy 23 le b 12 t 113 t 11,4 t *,13 13 a|13 1 131313 Figure I CFTR locus for brothers II-1 and II-4. Login to comment 107 ABCC7 p.Gly149Arg ABCC7 p.Ala800Gly ABCC7 p.Glu193Lys ABCC7 p.Glu193Lys C T A G G T A T G A A G-A T A G T T T A G ATC C C T C A a G C->G A A A C T T G E193K T C A C A T T G-A G A A T a C A ASOOG Figure 2 Autoradiographs showing nucleotide sequence of portions of exons 5, 13, and 4 of CFTR and demonstrating the mutations E193K, A800G, and G149R, respectively. Login to comment 117 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp These results show clearly that these two brothers are carrying two identical CFTR haplotypes and suggest that another locus could account for the phenotype observed for subject II,. Discussion mother of an affected child (Verlingue et al. 1993), her genotype being (R74W + D1270N) + 2183 AA--oG. If we consider that CBAVD may be a mild form of CF, these observations suggest that a second mutation in a CFTR allele may result in a reversion or partial reversion of phenotype. Login to comment 119 ABCC7 p.Arg553Gln Dork and coworkers (1991) identified an individual bearing both the AF508 and R553Q mutations on the same allele. Login to comment 135 ABCC7 p.Arg117His Further, a second mutation, R117H, known to lead to a mild phenotype in CF patients, was also found to occur at high frequency in these men (Gervais et al. 1993). Login to comment 162 ABCC7 p.Arg117His These genotypes could be considered extremely mild forms ofCF, the more frequent genotype forthis condition being AFS08/R117H. Login to comment 164 ABCC7 p.Arg117His (1993) that R117H occurs on two chromosomal backgrounds, one carrying a ST variant with respect to a polypyrimidine tract in intron 8, which alters exon 9 splicing, and the other carrying a 7T variant associated with normal exon 9 splicing. Login to comment 165 ABCC7 p.Arg117His The R117H mutations in this study are associated only with the 7T variant, indicating that the chromosomal background associated with CBAVD may be specific. Login to comment 166 ABCC7 p.Arg117His These data show that the CBAVD phenotype is determined by the association ofthe R117H with a particular chromosomal background. Login to comment