ABCMdb

PMID: 22395041

Uppaluri L, England SJ, Scanlin TF
Clinical evidence that V456A is a Cystic Fibrosis causing mutation in South Asians.
J Cyst Fibros. 2012 Jul;11(4):312-5. doi: 10.1016/j.jcf.2012.02.001. Epub 2012 Mar 5., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Val456Ala Genetic testing revealed that she is homozygous for the CFTR V456A mutation. Login to comment 6 ABCC7 p.Arg709* ABCC7 p.Val456Ala Patient 2, an Indian female diagnosed with CF on newborn screening, is compound heterozygous for V456A/R709X. Login to comment 9 ABCC7 p.Val456Ala Conclusions: We provide evidence that V456A can cause significant pulmonary disease in South Asian Cystic Fibrosis patients. Login to comment 10 ABCC7 p.Val456Ala Published by Elsevier B.V. Keywords: CF; V456A; Novel mutation; South Asian; Lung disease; Female; Delayed diagnosis 1. Login to comment 18 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala CF genetic analysis revealed that the patient was homozygous for V456A. Login to comment 84 ABCC7 p.Arg709* ABCC7 p.Val456Ala Subsequent genetic analysis showed that she was compound heterozygous for V456A and R709X. Login to comment 94 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala V456A is a mutation on exon 9 of CFTR resulting in T to C substitution at codon 456. Login to comment 109 ABCC7 p.Arg709* Subsequently it was suggested to be a mild disease causing mutation in adults with bronchiectasis and a new diagnosis of CF when heterozygous with delta F508 [14] and in females with delayed diagnosis of CF with mild disease [15] when heterozygous with R709X. Login to comment 111 ABCC7 p.Arg709* ABCC7 p.Val456Ala ABCC7 p.Val456Ala 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 ABCC7 p.Arg709* ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala 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 ABCC7 p.Val456Ala Formal proof that V456A is a CF disease causing mutation requires further investigation. Login to comment 118 ABCC7 p.Val456Ala However, our findings suggest that V456A Fig. 1. Login to comment