ABCMdb

PMID: 22366207

Haverkamp MH, van Wengen A, de Visser AW, van Kralingen KW, van Dissel JT, van de Vosse E
Pulmonary Mycobacterium abscessus: a canary in the cystic fibrosis coalmine.
J Infect. 2012 Jun;64(6):609-12. Epub 2012 Feb 23., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Arg117His After exclusion of genetic immune disorders known to cause NTM susceptibility, we found compound heterozygosity of two mutations, F508del and R117H in CFTR. Login to comment 51 ABCC7 p.Arg117His In the absence of defects in the IL-12/IFN-g pathway, we sequenced all 27 exons of the CFTR gene and found mutations in exon 10, c.1521-1523delCTT leading to F508del, and exon 4, c.482G>A leading to R117H (Fig. 1AeC). Login to comment 52 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His The length of a polythymidine stretch in intron 8, which precedes the exon 9 splice acceptor site, influences the amount of functional CFTR protein with the R117H mutation.5 We found 7 thymidines on the R117H allele (Fig. 1D). Login to comment 53 ABCC7 p.Arg117His ABCC7 p.Arg117His The length of a polythymidine stretch in intron 8, which precedes the exon 9 splice acceptor site, influences the amount of functional CFTR protein with the R117H mutation.5 We found 7 thymidines on the R117H allele (Fig. 1D). Login to comment 59 ABCC7 p.Arg117His Factor Examples Lung disorders COPD, fibrosis due to systemic diseases, malignancy Prior (lung) infections HIV, tuberculosis, NTM, histoplasmosis Genetic disorders Cystic fibrosis, a 1-antitrypsin deficiency, ciliary motility disorder, Lady Windermere Syndrome, MSMD Endocrine disorders Cushing Syndrome, panhypopituitarism Aspiration Hypersensitivity heterozygosity for F508del and R117H;T7 as in the patient. Login to comment 60 ABCC7 p.Arg117His ABCC7 p.Arg117His The other siblings were heterozygous for R117H;T7, but lacked the F508del mutation. Login to comment 61 ABCC7 p.Arg117His The other siblings were heterozygous for R117H;T7, but lacked the F508del mutation. Login to comment 65 ABCC7 p.Arg117His 6 Mild mutations in CFTR with residual function of the protein, like R117H, often appear in compound heterozygosity with F508del. Login to comment 66 ABCC7 p.Arg117His ABCC7 p.Arg117His R117H/F508del (estimated carrier rate 1/ 17,470 persons) can lead to adult onset isolated chronic pathology of the pulmonary, digestive or reproductive tracts (penetrance of delayed severe CF symptoms 0.06%), but also to classical childhood CF (penetrance 0.03%) or absence of all CF symptoms. Login to comment 67 ABCC7 p.Arg117His ABCC7 p.Arg117His 7 The activity of an R117H CFTR protein is further dependent on the length of a polythymidine stretch in intron 8. Login to comment 68 ABCC7 p.Arg117His Individuals with the R117H mutation and a T5 or T7 variant have lower levels of functional CFTR than individuals with T9 (the normal variant), because of reduced splicing of exon 9. Login to comment 69 ABCC7 p.Arg117His Individuals with the R117H mutation and a T5 or T7 variant have lower levels of functional CFTR than individuals with T9 (the normal variant), because of reduced splicing of exon 9. Login to comment 70 ABCC7 p.Arg117His 5 R117H;T7 has only recently been classified as a mutation that causes CF. Login to comment 71 ABCC7 p.Arg117His ABCC7 p.Arg117His 8 The broad clinical spectrum of F508del/R117H;T7, illustrated by genotypeephenotype relations in our patient`s relatives, makes genetic counseling difficult. Login to comment 72 ABCC7 p.Arg117His 8 The broad clinical spectrum of F508del/R117H;T7, illustrated by genotypeephenotype relations in our patient`s relatives, makes genetic counseling difficult. Login to comment 75 ABCC7 p.Arg117His 10,11 Mutations in CFTR, including F508del and R117H, are found in 36.5% of these patients, 10 but overall this seems to be a milder disease than even the attenuated forms of CF. Login to comment 76 ABCC7 p.Arg117His 10,11 Mutations in CFTR, including F508del and R117H, are found in 36.5% of these patients, 10 but overall this seems to be a milder disease than even the attenuated forms of CF. Login to comment 78 ABCC7 p.Arg117His Furthermore, childhood bronchitis, the cholecystectomy, infertility and her family history could have been interpreted as Figure 1 F508del, R117H and the length of a polythymidine stretch in intron 8 of the Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR). Login to comment 79 ABCC7 p.Arg117His Furthermore, childhood bronchitis, the cholecystectomy, infertility and her family history could have been interpreted as Figure 1 F508del, R117H and the length of a polythymidine stretch in intron 8 of the Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR). Login to comment 81 ABCC7 p.Arg117His The localization of the common F508del mutation in the first cytoplasmic Nucleotide Binding Domain and the milder R117H mutation in the first membrane spanning domain is indicated. Login to comment 82 ABCC7 p.Arg117His The localization of the common F508del mutation in the first cytoplasmic Nucleotide Binding Domain and the milder R117H mutation in the first membrane spanning domain is indicated. Login to comment 87 ABCC7 p.Arg117His The heterozygous missense mutation c.482G>A (R117H) in exon 4 leading to the replacement of Arginine (R) at residue 117 by Histidine (H). Login to comment 88 ABCC7 p.Arg117His The heterozygous missense mutation c.482G>A (R117H) in exon 4 leading to the replacement of Arginine (R) at residue 117 by Histidine (H). Login to comment