ABCMdb

PMID: 8473422

Patrizio P, Asch RH, Handelin B, Silber SJ
Aetiology of congenital absence of vas deferens: genetic study of three generations.
Hum Reprod. 1993 Feb;8(2):215-20., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* Four patients were found to be compound heterozygotes, three with genotypes Delta F-508/R117H, one with R553X/R117H. Login to comment 45 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* In six patients the mutation identified was W1282X, a nonsense mutation, localized on exon 20 and predicting the production of truncated polypeptides of CFTR; one patient was found to have the R553X mutation, a nonsense mutation of the CG to TG rule localized on exon 11; one patient had the mutation 1717G-A, localized on intron 10, which would cause defective RNA splicing; one patient was found to have the G542X mutation, a nonsense mutation in exon 11. Login to comment 46 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg553* Four of the 26 patients were found to be compound heterozygotes, three with genotypes Delta F508/R117H and one with R553X/R117H. Login to comment 47 ABCC7 p.Arg117His The mutation R117H was a missense mutation localized on exon 4. Login to comment 51 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr Exon 4,10,11,20 and 21 were amplified in a multiplex reaction followed by allele specific oligonucleotide (ASO) probe analysis for the mutations Delta F508, G542X, G551D, R553X, W1282X, N13O3K, Delta 1507, 1717G-A, R560T, S549N, R117H and 621 + 1. Login to comment 85 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Gly542* DF5O8/ DF5O8/ DF5O8/ DF508/ DF508/ DF508/ DF508/ DF5O8/ DF5O8/ DF5O8/ DF508/ DF5O8/ DF508/ W1282X/ W1282X/ W1282X/ W1282X/ W1282X/ DF508/R117H DF508/R117H DF508/R117H R553X/R117H R553X/ 1717G-A/ G542X/ Neg. NA NA NA NA DF508 NA NA NA Neg. NA NA NA NA Neg. NA NA NA DF508 NA R117H NA NA 1717G-A NA DF508 Neg. NA NA NA Neg. NA NA NA DF508 NA NA NA NA W1282X NA NA NA R117H NA DF508 NA NA Neg. NA Neg. Neg. NA NA NA Neg. NA Neg. Neg. Neg. Neg. Neg. Neg. NA Neg. NA Neg. Neg. Neg. NA R117H NA NA NA Neg. (g) DF508 - ... - - (g) Neg. - ... _. - - - - (b) Neg. - ... - - (g) DF5O8 (b) DF508 - - - (b) Neg. - b = boy; g = girl; NA = data not available; -, no offspring; DF5O8 = Delta F508. Login to comment 86 ABCC7 p.Trp1282* of the less common CF mutations were seen in significantly greater frequency in CAVD patients: W1282X had a frequency of 12% compared to <2% among CF patients, and Rl 17H had a frequency of 8% compared to < 1% in CF patients. Login to comment 89 ABCC7 p.Trp1282* Table I shows that of the eight mothers tested in the CAVD-CF+ group of patients, five were found to be carriers (one for Rl 17H, one for W1282X, and three for Delta F508). Login to comment 92 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* Cystic fibrosis (CF) mutation frequency in patients with CF and isolated bilateral congenital absence of vas deferens (CAVD) CF mutation Frequency in CF patients Frequency in CAVD CF positive patients R117H W1282X DF508 0.3% (3/812)a 1.6% (9/578) 73% (593/812) 8% (4/52) 12% (6/52) 31% (16/52) a (3/812) indicates three R117H alleles among 812 CF alleles (in 406 patients). Login to comment 95 ABCC7 p.Arg117His ABCC7 p.Arg553* R553X/R117H NA NA 2. Login to comment 96 ABCC7 p.Arg117His DF508/R117H3 DF508 R117H 3. Login to comment 97 ABCC7 p.Arg117His DF508/R117H NA NA 4. Login to comment 98 ABCC7 p.Arg117His ABCC7 p.Arg117His DF508/R117Ha R117H DF508 NA Neg. (g) DF508 Normal NA (b) DF508 Normal (+ vas) R117H - ??? Login to comment 113 ABCC7 p.Arg117His ABCC7 p.Arg117His Of the 28 wives tested, only one (3.6%) was found to be a carrier for a CF mutation (R117H), while her husband was a compound heterozygote (Delta F508/R117H). Login to comment 123 ABCC7 p.Arg117His ABCC7 p.Arg553* Of these, four patients were found to be compound heterozygotes, three with genotype Rl 17H/Delta F5O8 and one with R117H/R553X. Login to comment 127 ABCC7 p.Arg117His ABCC7 p.Gly542* However in the present study, we extended the genetic screening to the parents and the offspring of men with CAVD and moreover, by testing for 12 CF mutations, we demonstrated other rare CF mutations (R117H, G542X and 1717G-A) in patients with CAVD. Login to comment 129 ABCC7 p.Arg117His However, by analysing the results of genetic testing of fathers of patients with CAVD, we found four carriers for known CFTR mutations of which two carried Delta F508, one carried R117H and one 1717G-A. Login to comment 137 ABCC7 p.Arg553* In the four patients identified as compound heterozygotes for two CF mutations and whose only CF-related symptom is absence of the vas deferens, all have one Rl 17H mutation in combination with either Delta F508 (n = 3) or R553X mutations (n = 1). Login to comment 138 ABCC7 p.Arg117His Sweat chloride tests were only performed on two of the genotypes Delta F508/R117H and both were normal (40 and 45 mmol/1). Login to comment 139 ABCC7 p.Arg117His This is the first time that compound heterozygotes for Delta F508/R117H have been found to have normal sweat chloride tests and CAVD as the only phenotypical expression of CF disease. Login to comment 140 ABCC7 p.Arg117His 218 This finding is consistent with another report of mild CF cases involving Delta F508/R117H genotypes (Dean et al. Login to comment 141 ABCC7 p.Arg117His 1990) where it appears that the R117H mutation opposite Delta F508 may moderate the more severe phenotype of the homozygous Delta F508 genotype. Login to comment 144 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* The six CFTR mutations identified in this study occur on four exons plus one intron and represent deletion (Delta F508), nonsense (W1282X, 1717G-A and G542X) and amino acid substitution (R553X and R117H) mutations. Login to comment 145 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* R117H is one of the transmembrane regions of CFTR, Delta F508, W1282X and R553X are in nucleotide binding regions, and 1717G-A is at the splice border of intron 10 (Kerem et al., 1990; Cutting et al., 1990; Dean et al, 1990). Login to comment 147 ABCC7 p.Trp1282* Indeed, 1717G-A, Delta F508 and W1282X are associated with the pancreatic insufficient CF phenotype (Kerem et al., 1990) which tends to be a more severe phenotype, whereas Rl 17H has been found only in mildly affected individuals (Dean et al, 1990). Login to comment 148 ABCC7 p.Trp1282* ABCC7 p.Trp1282* Four of the six patients with the W1282X mutation were Jewish Ashkenazi and this is in agreement with a previous report where W1282X was found to be the most common CF mutation in this ethnic group (Shashani et al., 1992). Login to comment