ABCMdb

ABCC7 p.Val456Ala

None has been submitted yet.

Publications

PMID: 12357328 [PubMed] McCormick J et al: "Demographics of the UK cystic fibrosis population: implications for neonatal screening."

No. Sentence Comment

79 It is envisaged that the proposed screening programme will be based on a three-stage protocol.6 In Table 3 Genotypes of the UK CF Caucasian and ISC populations Percentage of Percentage of genotyped UK CF genotyped UK CF Caucasian population ISC population Genotype n=4753 (%) n=78 (%) DF508/DF508 57.5 24.7 DF508/Unknown 11.5 3.5 DF508/G551D 5.1 0.0 DF508/G542X 2.8 0.0 Unknown/Unknown 2.7 27.1 DF508/621+1G?T 2.0 1.2 DF508/R117H 2.0 0.0 DF508/1898+1G?A 1.0 0.0 DF508/1717-G?A 0.9 0.0 DF508/N1303K 0.8 0.0 DF508 DI507 0.8 0.0 DF508/R553X 0.6 0.0 DF508/R560T 0.6 0.0 DF508/Q493X 0.5 0.0 G551D/Unknown 0.4 0.0 Other/Other 2.8 15.3* DF508/Other 6.7 0.0 Y569D/Y569D 0.0 8.2 L218X/L218X 0.0 3.5 1161delC/1161delC 0.0 3.5 R709X/V456A 0.0 2.4 G542X/G542X 0.4 2.4 Other/Unknown 1.0 3.5 The shaded areas represent the commonest genotypes in the ISC population. Login to comment

PMID: 12544470 [PubMed] Strom CM et al: "Extensive sequencing of the cystic fibrosis transmembrane regulator gene: assay validation and unexpected benefits of developing a comprehensive test."

No. Sentence Comment

79 In the other patient, sequencing revealed homozygosity for a novel missense mutation V456A. Login to comment
90 Table 4 Results of sequencing of patient samples Description Prior genotype Sequencing CommentAllele 1 Allele 2 Confirmed CF wt/delta F508 delta F508 P205S Known mutation Confirmed CF wt/3849 ϩ 10 kb 3849 ϩ 10 kb L1077P Known mutation C 3 T C 3 T Confirmed CF wt/delta F508 delta F508 R1066C Known mutation Confirmed CF wt/delta F508 delta F508 D806G Novel missense Confirmed CF wt/wt 3154delG 3154delG Both parents confirmed carriers Confirmed CF delta F508/wt delta F508 G1244E Known mutation Confirmed CF wt/wt wt F191L Novel missense Borderline sweat test wt/wt wt wt Table 5 Resolution of ambiguities on linear array assay using sequencing Linear array result Resolution Weak mutant A455E line 1508 C 3 T (S459F) polymorphism or novel mutation Weak mutant A455E line 1508 C 3 T (S459F) polymorphism or novel mutation Weak mutant A455E line wt/1496 C 3 T (A455V) polymorphism or novel mutation Weak mutant A455E line wt/1496 C 3 T (A455V) polymorphism or novel mutation Weak mutant A455E line wt/1520 G 3 A (G463D) polymorphism or novel mutation No A455E mutant or wt line Homozygous 1499 T 3 C (V456A) polymorphism or novel mutation No A455E mutant or wt line Homozygous 1497 C 3 A polymorphism (no amino acid change) Weak wt 1898 ϩ 1 G 3 A line wt/E587A novel missense mutation or polymorphism Weak 1898 ϩ 1 G 3 A line wt/1898 ϩ 1 G 3 C-different mutation; G 3 C NOT G 3 A DISCUSSION The ACMG recommended panel of CF mutations has rapidly become the standard of care for US carrier screening. Login to comment

PMID: 14998948 [PubMed] Danziger KL et al: "Improved detection of cystic fibrosis mutations in infertility patients with DNA sequence analysis."

No. Sentence Comment

85 Cauc. Het. * DF508/R117H Mutation/mutation Yesd 7 CBAVD Asian-Indian Het. Negative Het. V456A Mutationc No 8 CBAVD Asian Negative * Het. Q1352H Mutation Nod 9 CBAVD Asian Negative * Negative No mutation detected Yes 10 CBAVDb N.E. Cauc./ Asian/Ashkenazi Negative * I556V/2752±26A®G Mutation/mutation Nod 11 CBAVD Hispanic Homozygous * Het. W1098C Mutation Nod 12 CBAVD Asian Negative Negative Het. 3499+25C®G Variant of unknown signi®cance No 13 CUAVD Hispanic Negative * Negative No mutation detected Yes 14 CBAVDb N.E. Cauc. Negative * Negative No mutation detected Yes 15 Idiopathic obstruction Asian-Indian Negative * Het. I807M Mutationc Nod 16 Idiopathic obstruction N.E. Cauc. Het. * Het. DF508 Mutation Yesd *Analysis not done. Login to comment
121 Mutations and variants of unknown signi®cance detected in 16 patients with CAVD Detection method 31 common mutation panel and poly T analysis Sequence method and poly T analysis Mutations 5T 7 7 DF508 2 2 R117H 1 1 P750L ± 1 V201M ± 1 Q1352H ± 1 I556V ± 1 2752±26A®G ± 1 W1098C ± 1 I807M ± 1 V456A ± 1 V520I ± 1 Variants of unknown signi®cance 1717±4A®G ± 1 3601±3C®A ± 1 3499+25C®G ± 1 Total 10 22 the vas deferens is particularly susceptible to the decreased levels of CFTR protein product. Login to comment
164 Mutation V456A (subject 7) has since been detected in three other symptomatic individuals, including: a Caucasian fetus with echogenic bowel, who has one other deleterious mutation, DF508; a Pakistani adult female with pulmonary symptoms and referred for CF testing who also harbors a DF508 mutation; and an Asian female infant with positive newborn screening and sweat tests, who has one other mutation, R709X. Login to comment
165 These clinical data from three compound heterozygotes provides compelling evidence that V456A is a genuine mutation. Login to comment

PMID: 17035430 [PubMed] Ziedalski TM et al: "Prospective analysis of cystic fibrosis transmembrane regulator mutations in adults with bronchiectasis or pulmonary nontuberculous mycobacterial infection."

No. Sentence Comment

11 Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Login to comment
94 Comparison of pulmonary function test data did not demonstrate significant differences between the Table 1-Subjects With Diagnosis of CF* Patient No. Age, yr Sex Bronch NTM† Other Infection‡ CFTR Mutations M470V Alleles IVS8 PolyT§ Sweat Chloride Level, mEq/dL 1 63 F Y MAC, Mch ⌬F508, I1027T 1 7T/9T 41 2 58 F Y MAC 2 7T/7T 65 3 66 F Y MAC, Mka PA 1 7T/7T 70 4 62 F Y MAC R75Q 2 5T/7T 67 5 53 F Y MAC G542X 0 5T/7T 60 6 74 F Y MAC SA ⌬F508, D1152H 1 9T/9T 46 7 33 F Y N PA ⌬F508, V456A 1 9T/9T 74 8 49 M Y N 1 7T/7T 77 9 73 F Y N S malto W1282X 1 7T/7T 63 10 52 F N Msi 2 2 7T/7T 68 *Bronch ϭ bronchiectasis (Bronch); F ϭ female; M ϭ male; Y ϭ yes; N ϭ no. Login to comment

PMID: 22395041 [PubMed] Uppaluri L et al: "Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South Asians."

No. Sentence Comment

5 Genetic testing revealed that she is homozygous for the CFTR V456A mutation. Login to comment
6 Patient 2, an Indian female diagnosed with CF on newborn screening, is compound heterozygous for V456A/R709X. Login to comment
9 Conclusions: We provide evidence that V456A can cause significant pulmonary disease in South Asian Cystic Fibrosis patients. Login to comment
10 Published by Elsevier B.V. Keywords: CF; V456A; Novel mutation; South Asian; Lung disease; Female; Delayed diagnosis 1. Login to comment
18 Here we present the clinical course of 2 patients with one such novel mutation (V456A), who have been diagnosed with CF pulmonary disease. Login to comment
74 CF genetic analysis revealed that the patient was homozygous for V456A. Login to comment
84 Subsequent genetic analysis showed that she was compound heterozygous for V456A and R709X. Login to comment
94 Discussion We present the clinical courses of two females of South Asian descent, one homozygous and one compound heterozygous for the V456A mutation. Login to comment
97 Both of our patients with the V456A genotype have low BMI's with normal pancreatic function and lung disease associated with low FEV1, FVC and FEV1/FVC, phenotypical findings consistent with previous literature. Login to comment
106 V456A is a mutation on exon 9 of CFTR resulting in T to C substitution at codon 456. Login to comment
111 V456A is not a common genotype with only 2.4% of 78 South Asian patients exhibiting the V456A/R709X genotype in the genotyped UK population [16]. Login to comment
112 Danziger et al. [17] suggested that V456A is a disease causing mutation based on pathology in 4 heterozygous patients with this mutation but 2 of these patients had delta F508 mutations, one was heterozygous for R709X, and the other heterozygous for an unidentified mutation. Login to comment
113 Ambry Genetics and ARUP Laboratories (personal communications) have identified only 3 homozygous patients with V456A and 8 heterozygous patients with this mutation, including our 2 patients described here. Login to comment
114 Thus it is impossible to conclude with certainty that V456A is a disease causing mutation until further investigations confirm this suggestion using the criteria recommended in the Cystic Fibrosis Foundation consensus report [18]. Login to comment
115 We conclude that these cases provide clinical evidence that V456A is not just a mild polymorphism but a CF disease causing mutation in South Asians. Login to comment
117 Formal proof that V456A is a CF disease causing mutation requires further investigation. Login to comment
118 However, our findings suggest that V456A Fig. 1. Login to comment

PMID: 22423042 [PubMed] Gonska T et al: "Role of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in patients with chronic sinopulmonary disease."

No. Sentence Comment

66 All P values are two-sided with a Table 2-CFTR Genotypes Identified in Subjects With Idiopathic Sinopulmonary Disease CF Causing/CF Causing CF Causing/CFTR Mutation CFTR Mutation/CFTR Mutation CF Causing/Unknown CFTR Mutation/Unknown F508del/A455E 3x F508del /D1152H 2x D579G/D579G 2x F508del /26x R764X/2 F508del/S1251N R75X/V456A 758delC/2 F508del/L967S 1716G.A/5T 1716G.A/2 F508del/5T R75Q/5T R117H (7T)/23x F508del/3212T.C 5T/23x G542X/D1152H 1717-1G.A/Q1291H Patients are grouped according to the identified CFTR alterations on allele 1/allele 2. Login to comment

PMID: 24149827 [PubMed] Ooi CY et al: "Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?"

No. Sentence Comment

127 ߤ14/24 (58%) were not identified with two CF-causing mutations: 12 carried one CF-causing mutation (DF508/-(x5); DF508/5 T (x3); DF508/D1152H; R75X/V456A; 1717-1G>A/Q1291H; 1717-1G>A/5 T) and two had no CF-causing mutation (D579G/D579G; -/-). Login to comment

PMID: 25651269 [PubMed] Mazumdar M et al: "Elevated sweat chloride levels due to arsenic toxicity."

No. Sentence Comment

46 Age Male Sex Smoking Status History of Skin Lesions Sweat Conductivity Sweat Chloride Arsenic in Drinking Water Arsenic in Fingernails FEV 1 CFTR Sequencing At Enrollment (2001-2003) At Follow-up (2007-2009) Currently (2013-2014) At Enrollment (2001-2003) At Follow-up (2007-2009) Currently (2013-2014) Reportable Variantߤ yr mmol/liter &#b5;g/liter &#b5;g/g % ߒ1 55 No Never No 75 62 431.0 420.0 155.7 14.08 17.83 20.86 97 p.I807 M (c.2421A࢐G) ߒ2 28 Yes Current No 69 63 88.3 - 151.9 9.42 - 12.52 87 p.V456A (c.1367T࢐C) ߒ3 33 Yes Previous No 86 63 24.2 150.0 12.0 4.00 1.30 1.69 85 c.3469-20T࢐C ߒ4 40 Yes Never Yes 98 66 38.6 69.0 8.9 9.85 1.90 3.07 51 c.4243-16A࢐G ߒ5 30 Yes Never Yes 76 68 535.0 43.0 19.4 11.86 11.81 12.99 89 No mutations ߒ6 38 Yes Current No 76 69 1.1 - 60.6 9.64 - 11.61 77 12/5T; 10/9Tߥ ߒ7 55 Yes Current Yes 74 70 661.0 30.0 0.4 18.28 10.84 26.48 114 No mutations ߒ8 58 Yes Previous Yes 58 72 553.0 900.0 1.1 19.42 29.43 12.83 80 No mutations ߒ9 37 Yes Never No 83 75 33.0 11.0 1.8 3.47 4.15 4.71 78 No mutations 10 42 Yes Current Yes 88 76 697.0 920.0 0.9 24.06 45.19 5.86 54 No mutations 11 65 Yes Previous Yes 84 78 839.0 - 15.2 15.72 15.95 11.54 104 No mutations * FEV 1 denotes forced expiratory volume in 1 second, and dashes indicate that the participant was not evaluated in a 2007-2009 follow-up study. Login to comment