ABCMdb

PMID: 15520400

Niel F, Martin J, Dastot-Le Moal F, Costes B, Boissier B, Delattre V, Goossens M, Girodon E
Rapid detection of CFTR gene rearrangements impacts on genetic counselling in cystic fibrosis.
J Med Genet. 2004 Nov;41(11):e118., [PubMed]

Sentences

No. Mutations Sentence Comment

136 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Asn1303Lys ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Ser945Leu ABCC7 p.Arg668Cys ABCC7 p.Gly576Ala ABCC7 p.Asp443Tyr ABCC7 p.Leu997Phe ABCC7 p.Asp110His The subjects were divided into three groups according to the results of a previous screening: (i) 43 CF patients who fulfilled the diagnostic criteria of CF15 and who carried a CF mutation, and seven parents of deceased CF patients, a CF mutation having already been identified in the other parent (50 unidentified CF alleles); (ii) 12 CF patients with no identified CF mutation (24 unidentified CF alleles); and (iii) 16 patients apparently homozygous for a CFTR mutation and who had CF (F508del 2n = 6-, 2104insA22109del10, S945L, 3120+1GRA, N1303K) or a CFTR related disease, that is, isolated CBAVD (D110H, R117H, L997F, R74W-D1270N) or DB (R334W, R668C- G576A-D443Y) (0-16 unidentified CF alleles). Login to comment 184 ABCC7 p.Arg117His One further rearrangement was identified in the third group of 16 patients, in a CBAVD patient who was apparently R117H homozygous. Login to comment 192 ABCC7 p.Val754Met The former was found in cis with the V754M variation (exon 13), which has been described as a CF mutation (www.genet. sickkids.on.ca/cftr). Login to comment 193 ABCC7 p.Arg117His ABCC7 p.Arg117His The complete deletion was identified in a patient having CBAVD, and who apparently carried two R117H-7T copies (R117H in cis with the IVS8-7T variant). Login to comment 194 ABCC7 p.Arg117His Posterior analysis of his parents confirmed the compound heterozygosity for R117H and the deletion. Login to comment 207 ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Ala561Glu Gender Current age Phenotype Genotype Origin Age at diagnosis Pancr. status Lung disease Other Sweat test Allele 1 Allele 2 rearrangement involving exon(s) Parental Geographic 1 M 10 years 1 month PI Severe 114 F508del 1 Father North eastern Italy 2 M 16 years Birth PI Severe 130 A561E 2 Father Southern Italy 3 M 10 years 1 year PI Severe + R553X 17b Mother France 4 F 13 years 4 years PI Severe NP + F508del 14b-17b Father Eastern France 5 F 24 years 1 month PI Severe 100 F508del 17a-17b Mother ND 6 F 21 years Childhood PI Moderate + F508del 17a-17b Father Eastern France 7 M 35 years 1 year PI Severe CBAVD, NP 103 F508del 17a-17b Father Eastern France 8* 2 F Deceased at 2 and 6 months Birth PI Severe ND F508del 17a-17b Father Eastern France 9 F Deceased at 15 years 5 years PI Severe 300 1812- 1GRA 3-10,14b-16À Mother Kabylie (Algeria)/ Brittany (France) 10 M 37 years 37 years PS None CBAVD ND R117H(-7T) 1-24 Mother France 11 M Deceased at 31 years 3 months PI Severe DB 90 G542X 4-8 Mother Eastern France CBAVD, congenital bilateral absence of the vas deferens; DB, disseminated bronchiectasis; del, deletion; dup, duplication; F, female; M, male; NP, nasal polyposis; Pancr., pancreatic; PI, pancreatic insufficiency; PS, pancreatic sufficiency. Login to comment 209 ABCC7 p.Val754Met ÀThe CFTRdele3-10,14b-16 deletion was identified in cis with the V754M variation. Login to comment 237 ABCC7 p.Gly542* **The linked haplotype was hypothesised, considering the most frequent haplotype IVS8(CA)23-IVS17b(TA)33-IVS17b(CA)13 linked to G542X.43 Considering the CFTR deletions already described and those we report here, it clearly appears that some CFTR sequences may be prone to rearrangements. Login to comment 251 ABCC7 p.Arg117His ABCC7 p.Arg117His In the particular case of patient no. 10, we considered that a R117H-7T homozygous genotype could not explain the CBAVD phenotype and suspected rather the presence of a severe CF anomaly in trans of R117H. Login to comment 253 ABCC7 p.Arg74Trp ABCC7 p.Leu997Phe In other respects, the proven homozygous genotype for mild CFTR mutations found in CBAVD or DB patients of the third group, such as R74W-D1270N33 or L997F,6 34-36 is not considered as deleterious enough to account for their disease. Login to comment 256 ABCC7 p.Val754Met We considered a possible complex allele in patient no. 9, on a V754M background, as the corresponding part of the R domain is not well conserved among species, residue V754 being a valine in primates but a methionine in rabbit and mouse species. Login to comment 257 ABCC7 p.Val754Met In addition, residue V754 is not located in the refined functional R domain.37 V754M was described as a CF mutation, as it was found in a patient having classical CF (www.genet.sickkids.on.ca/cftr). Login to comment 258 ABCC7 p.Val754Met ABCC7 p.Val754Met ABCC7 p.Val754Met The identification of the complex CFTRdele3-10,14b-16 in cis with V754M thus leads to the reconsideration of V754M as probably not disease causing, which will reassure individuals studied for carrier screening who are V754M heterozygotes but do not carry any other mutation/deletion. Login to comment