ABCMdb

PMID: 10200050

de Meeus A, Guittard C, Desgeorges M, Carles S, Demaille J, Claustres M
Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online.
Hum Mutat. 1998;11(6):480., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Ala1067Thr Fourty-two of the 64 patients (65.6%) had mutations on both copies of the CFTR gene, including one patient with two mutations in the same copy (DF508 + A1067T). Login to comment 8 ABCC7 p.Pro111Leu ABCC7 p.Ala1364Val ABCC7 p.Gly544Val ABCC7 p.Met244Lys Six of the 28 different mutations identified in this study had never been described previously, and appeared to be specific to CBAVD (P111L, M244K, A1364V, G544V, 2896insAG, -33G->A). Login to comment 31 ABCC7 p.Ala1067Thr A double mutant allele was identified in one CBAVD patient (N°38 in table 1) with the DF508 associated to the mutation A1067T on the same chromosome inherited from his father, in trans with the 5T allele inherited from his mother. Login to comment 32 ABCC7 p.Pro111Leu ABCC7 p.Ala1364Val ABCC7 p.Gly544Val ABCC7 p.Met244Lys Four of the novel mutations are missense mutations (P111L, M244K, A1364V, G544V), one is an insertion/frameshift (2896insAG), and one is located in the 5' upstream promoter region (-33G-%gt;A). Login to comment 33 ABCC7 p.Pro111Leu P111L is caused by a transition C->T at nucleotide 464, and results in the replacement of a proline by a leucine in the middle part of the first extracytoplasmic loop connecting the membrane spanning domains TM1 and TM2. Login to comment 37 ABCC7 p.Met244Lys M244K is due to T->A transversion at nucleotide 863 in exon 6a, that changes the non polar, hydrophobic methionine residue to the positively charged lysine. Login to comment 39 ABCC7 p.Ala1364Val ABCC7 p.Met244Lys M244K is the second of a stretch of 3 methionine residues at the begining of the intracytoplasmic loop between TM4 and TM5. A1364V is caused by C->T substitution at nucleotide 4223 in exon 22. Login to comment 41 ABCC7 p.Gly544Val G544V is due to a G->T substitution at nucleotide 1763 in exon 11, creating a Mme1 restriction site. Login to comment 50 ABCC7 p.Asp443Tyr ABCC7 p.Pro111Leu ABCC7 p.Ala1364Val ABCC7 p.Gly544Val ABCC7 p.Met244Lys These mutations can also be found in the CF patients from our area, except seven (D443Y, M244K, P111L, A1364V, G544V, 2896insAG and -33G->A) which appear to be specific to CBAVD. Login to comment 56 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg347His ABCC7 p.Leu206Trp ABCC7 p.Asp1152His ABCC7 p.Asp1152His However, some genotypes (DF508/L206W, DF508/R347H, DF508/D1152H, DF508/R117H, W1282X/D1152H and even DF508/5T) can induce both CF and CBAVD phenotypes. Login to comment 58 ABCC7 p.Arg117His As the level of CFTR mRNA lacking exon 9 are determined by the variation at locus IVS8(T)n, the mutation R117H can cause CF with pancreatic sufficiency (CF-PS) or obstructive azoospermia, depending on the polyT allele of intron 8 that is associated (5T in CF-PS and 7T in CBAVD) (Kiesewetter et al. 1993). Login to comment 63 ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln The variability of the phenotypic expression could also be explained in some cases by the presence of an additional mutation in the CFTR gene, as it has been reported for the double mutant DF508-R553Q in which the R553Q mutation compensates the deleterious effect of the DF508 deletion (Dork et al. 1991). Login to comment 83 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly1244Glu ABCC7 p.Gly1349Asp ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Arg347His ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Leu206Trp ABCC7 p.Leu206Trp ABCC7 p.Tyr1092* ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Asp1152His ABCC7 p.Lys710* ABCC7 p.Met952Ile ABCC7 p.Phe508Cys ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Asp443Tyr ABCC7 p.Arg764* ABCC7 p.Pro111Leu ABCC7 p.Ala1364Val ABCC7 p.Gly544Val ABCC7 p.Met244Lys Phenotype CFTRamutations Intron 8, Poly(T) tract 1 3 crisis of acute pancreatitis F508 / L206W 9/7 2 F508 / L206W 9/9 3 frequent bronchitis F508 / R347H 9/9 4 F508 / R347H 9/9 5 F508 / M244K 9/7 6 F508 / A1364V 9/7 7 F508 / D1152H 9/7 8 chronic sinusitis and bronchitis F508 / D1152H 9/7 9 F508 / R117H 9/7 10 F508 / R117H 9/7 11 F508 / M952I 9/7 12 D443Y / G542X 7/9 13 D443Y / G542X 7/9 14 2184delA / D443Y 7/7 15 2184delA / D443Y 7/7 16 R347H / D443Y 9/7 17 seminal vesicles agenesia R117H / G1349D 7/7 18 R117H / G1244E 7/7 19 N1303K / P111L 9/7 20 chronic sinusitis, nasal polyps W1282X / D1152H 7/7 21 chronic sinusitis R347H / Y1092X 7/7 22 seminal vesicles agnesia 297-3C-GTT / 4279insA 7/7 23 G544V / F508C 7/7 24 D1152H / 2896insAG 7-9 25 F508 / - 9/5 26 F508 / - 9/5 27 F508 / - 9/5 28 F508 / - 9/5 29 F508 / - 9/5 30 chronic sinusitis, bronchitis F508 / - 9/5 31 sinusitis and allergy F508 / - 9/5 32 allergy F508 / - 9/5 33 F508 / - 9/5 34 F508 / - 9/5 35 F508 / - 9/5 36 F508 / - 9/5 37 bronchitis, asthma F508 / - 9/5 38 chronic sinusitis F508+A1067T / - 9/5 39 chronic sinusitis D1152H / - 7/5 40 2184delA / - 7/5 41 R764X / - 7/5 42 711+1G-GTT / - 7/5 43 F508 / - 9/7 44 F508 / - 9/7 45 F508 / - 9/7 46 F508 / - 9/9 47 R553X / - 7/7 48 -33G-GTA / - 7/7 49 K710X / - 7/7 50 - / - 5/5 51 - / - 5/7 52 - / - 5/7 53 - / - 7/7 54 - / - 7/7 55 - / - 7/7 56 - / - 7/7 57 - / - 7/7 58 - / - 7/7 59 - / - 7/7 60 - / - 7/7 61 - / - 7/9 62 - / - 7/9 63 NIDDb - / - 7/9 64 - / - 7/9 a : Cystic Fibrosis Transmembrane Regulator gene b : Non Insulino-Dependant Diabetis References Anguiano A, Oates RD, Amos JA, Dean M, Gerrard B, Stewart C, Maher TA, White MB, Milunsky A (1992) Congenital absence of the vas deferens: a primarily genital form of cystic fibrosis. 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