ABCMdb

PMID: 18394117

Lee TW, Conway SP, Peckham D, Brownlee KG
Respiratory exacerbations in childhood associated with compound heterozygosity Phe508del/Arg117His-7T of the cystic fibrosis transmembrane regulator gene.
Acta Paediatr. 2008 May;97(5):670-2., [PubMed]

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No. Mutations Sentence Comment

2 ABCC7 p.Arg117His DOI:10.1111/j.1651-2227.2008.00716.x Abstract Debate continues regarding the clinical implications for compound heterozygotes identified with Phe508del and Arg117His-7T mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. Login to comment 4 ABCC7 p.Arg117His Conclusion: The compound heterozygote cystic fibrosis (CF) mutation Phe508del with Arg117His-7T should not necessarily be considered benign in childhood. Login to comment 11 ABCC7 p.Arg117His Consequently, for many mutations such as Arg117His-7T it remains unclear whether they should be screened for, how intensive monitoring and treatment should be and what information about prognosis should be given. Login to comment 12 ABCC7 p.Arg117His ABCC7 p.Arg117His Scotet et al. have recently suggested that Arg117His should be removed from the newborn screening mutation panel, as in their experience compound heterozygotes with Arg117His-7T remain asymptomatic in childhood (5). Login to comment 13 ABCC7 p.Arg117His We present a case with significant respiratory complications in early childhood, in whom Arg117His-7T was identified (compound heterozygote with Phe508del). Login to comment 25 ABCC7 p.Arg117His Mutation screen for 32 common CFTR gene mutations identified her as a compound heterozygote for Phe508del and Arg117His mutations on a background of a polythymidine tract of 9T/7T at intron 8. Login to comment 36 ABCC7 p.Arg117His ABCC7 p.Arg117His DISCUSSION It has been suggested that Arg117His with a 7T allele should not be considered as a true CF mutation in the presence of a 670 C 2008 The Author(s)/Journal Compilation C 2008 Foundation Acta Pdiatrica/Acta Pædiatrica 2008 97, pp. 663-672 Lee et al. Respiratory exacerbations with R117H-T CF mutation Figure 1 Chest X-ray demonstrating significant respiratory exacerbation with right middle lobe and lower lobe collapse and consolidation, with additional patchy consolidation bilaterally. Login to comment 39 ABCC7 p.Arg117His Arg117His is an exon 4 missense mutation, which results in a full length of normally processed protein, but with reduced function at the cell membrane. Login to comment 43 ABCC7 p.Arg117His ABCC7 p.Arg117His Arg117His on a 5T background is associated with moderate-to-severe pancreatic-sufficient CF, however, Arg117His-7T can be associated with normal sweat electrolytes and some groups have suggested that it should not therefore be considered a CF causing mutation (6-8). Login to comment 48 ABCC7 p.Arg117His ABCC7 p.Arg117His Scotet et al. (2006), describing compound heterozygotes with Arg117His-7T identified through the newborn screening programme in Brittany, France, reported that none of the nine children had developed any signs of CF by a mean age of 7 years, and argued that Arg117His should be removed from the newborn screening mutation panel (5). Login to comment 51 ABCC7 p.Arg117His Lording et al. (2006) describe a series of children who are compound heterozygous for Arg117His with the 7T allele and conclude that most children with this genotype have bacterial isolates from routine airway cultures that require antibiotic therapy three to four times a year (12). Login to comment 52 ABCC7 p.Arg117His Similarly, Massie et al. (2001) have described three children, compound heterozygote Arg117His with 7T, who had borderline sweat tests and recurrent cough (13). Login to comment 53 ABCC7 p.Arg117His O`Sullivan et al. (2006) described four cases of Phe508del with Arg117His-7T identified through newborn screening in Massachusetts USA (14). Login to comment 55 ABCC7 p.Arg117His Although variation in genes other than the CFTR gene can cause CF-like symptoms (15), our paper provides additional evidence that significant respiratory exacerbations can be associated with Arg117His-7T in childhood. Login to comment 56 ABCC7 p.Arg117His CONCLUSION Mild CF mutations such as Arg117His-7T are associated with less rapidly progressive lung disease but are not necessarily benign. Login to comment