ABCMdb

PMID: 10980579

Bombieri C, Luisetti M, Belpinati F, Zuliani E, Beretta A, Baccheschi J, Casali L, Pignatti PF
Increased frequency of CFTR gene mutations in sarcoidosis: a case/control association study.
Eur J Hum Genet. 2000 Sep;8(9):717-20., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC7 p.Arg347Pro ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe ABCC7 p.Ile991Val ABCC7 p.Gly1069Arg Seven different CFTR gene mutations were observed: R75Q, R347P, 621 + 3 A/G, 1898 + 3 A/G, L997F, G1069R, and a novel mutation which was detected in this study, I991V. R75Q mutation was present in 3/26 patients, a significant increase (P = 0.01) in cases over controls, indicating its preferential association with sarcoidosis. Login to comment 33 ABCC7 p.Arg347Pro ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe ABCC7 p.Ile991Val ABCC7 p.Gly1069Arg Seven different missense or splicing mutations were found in the eight patients: R75Q, R347P, 1898 + 3 A/G, 621 + 3 A/G, L997F, G1069R, I991V. R75Q was present in three patients (nos. 15, 21, 27). Login to comment 35 ABCC7 p.Arg75Gln R75Q has been described in CF and related diseases, as disseminated bronchiectasis,7,16 and allergic broncho-pulmonary aspergillosis.17 One patient (no. Login to comment 36 ABCC7 p.Arg75Gln 15) had two CFTR mutations (R75Q, 1898 + 3 A/G), but it was not possible to determine the phase. Login to comment 37 ABCC7 p.Arg347Pro ABCC7 p.Leu997Phe ABCC7 p.Gly1069Arg R347P is known to cause CF.18 1898 + 3 A/G has been found in 1/225 genes from an Italian CF birth cohort we have previously described.19 The mutation 1898 + 3 A/G abolishes the donor splice site (program cited in methods), with the possible consequence of exon 12 skipping from mature mRNA. 621 + 3 A/G, L997F, and G1069R have been described in rare CF cases (Cystic Fibrosis Genetic Analysis Consortium website: http:/ /www.genet.sickkids.on.ca). Login to comment 38 ABCC7 p.Leu997Phe ABCC7 p.Ile991Val Mutation 621 + 3 A/G abolishes the donor splice site (program cited in Methods), with the possible consequence of exon 4 skipping from mature mRNA. L997F was found also in disseminated bronchiectasis.7,16 I991V is a novel mutation here described for the first time: it changes isoleucine to valine (both hydrophobic residues) in the second transmembrane domain. Login to comment 45 ABCC7 p.Arg347Pro ABCC7 p.Val754Met ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe ABCC7 p.Ile991Val ABCC7 p.Gly1069Arg With the exception of two novel mutations, E826K7 and I991V (this study), all the mutations present in the 34 patients with sarcoidosis (R75Q, 621 + 3 A/G, R347P, DF508, 1898 + 3 A/G, V754M, L997F, G1069R, 4382 del A) have also been observed in CF and CF-related diseases. Login to comment 46 ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe Two recurrent mutations were observed in sarcoidosis: R75Q found in 3/34 patients and in 0/89 controls (P = 0.02), and L997F found in 2/34 patients and in 0/89 controls (NS). Login to comment 47 ABCC7 p.Arg75Gln R75Q may therefore be a CFTR gene mutation characteristic of sarcoidosis. Login to comment 52 ABCC7 p.Arg347Pro ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Leu997Phe ABCC7 p.Ile991Val ABCC7 p.Gly1069Arg Sarcoidosis is a complex disease in which genetic and environmental factors may play Table 2 CFTR genotypes of sarcoidosis patients (n = 26) Missense and Same sense and ID splicing mutations intronic mutations TGm-Tn M470V 11 G1069R 11-7/12-7 V/V 13 R347P 4404 C/T 10-7/11-7 M/V 15 R75Q, 1898+3A/G 186-13 C/G 11-7/11-7 V/V 20 621+3 A/G 10-7/10-7 M/M 21 R75Q 11-7/11-7 V/V 27 R75Q 1716 G/A 10-7/11-7 M/V 31 I991V 11-7/10-9 M/V 32 L997F 4002 A/G, 3041-71 G/C 10-9/11-9 M/V 10 4404 C/T 11-7/11-7 V/V 18 4002 A/G 11-7/12-7 M/V 24 3417 A/T 11-7/11-7 V/V 28 4002 A/G 11-7/11-7 M/V 34 4002 A/G 11-7/11-7 M/V 26 12-5/11-7 V/V 16 12-5/11-7 V/V 9 11-7/11-7 V/V 12 12-7/10-9 M/M 14 11-7/10-9 M/V 17 11-7/11-7 V/V 19 11-7/10-9 M/V 22 10-7/11-7 M/V 23 10-7/11-7 M/V 25 10-7/11-7 M/V 29 11-7/11-9 M/V 30 11-7/11-7 V/V 33 11-7/12-7 V/V The phase of the mutations is not known, as no segregation analysis was possible. Login to comment