ABCC7 p.Ala457Pro
| Predicted by SNAP2: | C: N (53%), D: D (91%), E: D (71%), F: D (91%), G: D (75%), H: D (91%), I: D (53%), K: D (75%), L: D (63%), M: D (59%), N: D (85%), P: D (75%), Q: D (85%), R: D (91%), S: N (66%), T: N (66%), V: N (66%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | C: N, D: D, E: N, F: N, G: D, H: D, I: N, K: N, L: N, M: N, N: D, P: N, Q: N, R: D, S: N, T: N, V: N, W: D, Y: N, |
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[hide] The Novel CFTR Mutation A457P in a Male with a Del... Case Report Med. 2011;2011:903910. Epub 2011 Dec 13. Cole KH, Sosnay PR, Yarmus LB, Zuckerman JB
The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis.
Case Report Med. 2011;2011:903910. Epub 2011 Dec 13., [PMID:22194755]
Abstract [show]
Cystic fibrosis (CF) is an autosomal recessive disease that may be caused by more than 1000 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the case of a CF patient who was initially diagnosed at 16 years of age after presenting with mild respiratory compromise and pancreatic sufficiency. When genetic testing was first performed using a CF mutation panel, only a single F508del CFTR allele was identified. We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C). The patient's clinical course through adulthood is described, and genotype-phenotype correlation is discussed. The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV-VI defects. With the advent of more comprehensive and widely available genetic testing techniques, identification of CF genotypes in patients with milder disease variants may help stratify patients for targeted therapy and prevent late complications of the disease.
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No. Sentence Comment
0 Hindawi Publishing Corporation Case Reports in Medicine Volume 2011, Article ID 903910, 4 pages doi:10.1155/2011/903910 Case Report The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis Kate H. Cole,1 Patrick R. Sosnay,1 Lonny B. Yarmus,1 and Jonathan B. Zuckerman2 1 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 1830 East Monument Street, 5th Floor, Baltimore, MD 21208, USA 2 Division of Pulmonary and Critical Care Medicine, Maine Medical Center, 22 Bramhall Street, Portland, ME 04102, USA Correspondence should be addressed to Jonathan B. Zuckerman, zuckej@mmc.org Received 16 August 2011; Revised 21 September 2011; Accepted 25 September 2011 Academic Editor: Mamede de Carvalho Copyright (c) 2011 Kate H. Cole et al.
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ABCC7 p.Ala457Pro 22194755:0:156
status: NEW5 We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C).
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ABCC7 p.Ala457Pro 22194755:5:84
status: NEWX
ABCC7 p.Ala457Pro 22194755:5:93
status: NEW7 The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV-VI defects.
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ABCC7 p.Ala457Pro 22194755:7:4
status: NEW14 After transfer of care to our institution, a full-sequence CFTR genetic analysis was performed by Ambry Genetics, which revealed an A457P mutation in combination with the F508 deletion.
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ABCC7 p.Ala457Pro 22194755:14:132
status: NEW15 We briefly describe the clinical profile of this patient with the A457P mutation, discuss the established criteria used to diagnose CF, and speculate about the possibility that this newly identified variant is a disease-causing mutation.
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ABCC7 p.Ala457Pro 22194755:15:66
status: NEW49 Testing revealed an A457P mutation in exon 10 in combination with the F508 deletion.
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ABCC7 p.Ala457Pro 22194755:49:20
status: NEW51 A literature review and examination of the Sick Kids Cystic Fibrosis Mutation database revealed no prior report of the A457P mutation [10].
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ABCC7 p.Ala457Pro 22194755:51:119
status: NEW69 Analysis of the previously unidentified genetic variation A457P must be considered in the context of its discovery in an individual with an established diagnosis of CF.
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ABCC7 p.Ala457Pro 22194755:69:58
status: NEW75 Given that CF is an autosomal recessive disease and that our patient is an affected individual, it would appear that A457P is a CF-causing mutation in this instance.
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ABCC7 p.Ala457Pro 22194755:75:117
status: NEW78 Therefore, it is possible, although unlikely, that another mutation is present on the A457P chromosome, for example, in an intronic region that may not have been sequenced.
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ABCC7 p.Ala457Pro 22194755:78:86
status: NEW79 When entered into publicly available in silico mutation prediction tools PolyPhen [13] and SIFT [14], the A457P mutation, which resides within the nucleotide binding domain 1 of the CFTR, was predicted to be deleterious; however, these methods have not shown adequate sensitivity or specificity in CF to have clinical utility [15].
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ABCC7 p.Ala457Pro 22194755:79:106
status: NEW80 Taken together, these findings argue for A457P being a disease-causing mutation, though it is still most accurate to formally categorize it as a VUS.
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ABCC7 p.Ala457Pro 22194755:80:41
status: NEW90 Our patient`s presentation of mild respiratory symptoms and pancreatic sufficiency in association with one known Class II mutation suggests that A457P is likely a Class IV-VI mutation (i.e., one that retains some chloride channel function).
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ABCC7 p.Ala457Pro 22194755:90:145
status: NEW91 Functional testing could help elucidate the cellular consequences of the A457P substitution to support the hypothesis that the mutation is deleterious and to assign the mutation to a functional class; however, the considerable resources necessary to perform such confirmatory work would generally make this impractical for a mutation found in a single patient.
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ABCC7 p.Ala457Pro 22194755:91:73
status: NEW94 Detailed genetic analysis revealed that he carries the novel mutation (A457P) along with the most common CFTR mutation (F508del).
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ABCC7 p.Ala457Pro 22194755:94:71
status: NEW