Mutation Analysis of the <i>CFTR</i> Gene in 225 Children: Identification of Five Novel Severe and Seven Reported Severe Mutations

Sachdeva, Kabir; Saxena, Renu; Puri, Ratna Dua; Bijarnia, Sunita; Kohli, Sudha; Verma, Ishwar C.

doi:10.1089/gtmb.2011.0283

Cited by 16 publications

(12 citation statements)

References 21 publications

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“…Recent years have seen publication of genetic and mutation profiles for large case series of osteogenesis imperfecta, skeletal dysplasias, and lysosomal storage disorders. These studies have revealed the unique molecular profile of patients from the India with identification of many novel mutations not previously reported in other populations (Gorospe et al 2004;Pathak et al 2010;Sachdeva et al 2011Sachdeva et al , 2012Shukla et al 2011;Bashyam et al 2012;Dalal et al 2012;Mistri et al 2012;Bidchol et al 2014;Ankala et al 2015;Stephen et al 2015; A. Uttarilli, P. Ranganath, S.J.M. Nurul Jain, K.P.…”

Section: Academic Programs In Medical Geneticsmentioning

confidence: 93%

“…Use of SNP microarray to identify regions of homozygosity and candidate genes in these regions is a strategy which can be successfully used in the consanguineous families (Stephen et al 2015). Some conditions found to be relatively common have been Van Der Knaap disease with a founder mutation in the Agarwal community from north western India, calpainopahy, recessive forms of Osteogenesis imperfecta, Progressive pseudorheumatoid arthropthy of childhood and Handigodu disease from a specific community in South India (Gorospe et al 2004;Pathak et al 2010;Sachdeva et al 2011Sachdeva et al , 2012Shukla et al 2011;Bashyam et al 2012;Dalal et al 2012;Bidchol et al 2014;Ankala et al 2015). However, the available data on monogenic malformation syndromes and metabolic disorders from India though extensive, represents only tip of the iceberg as a large population still does not have access to the clinical genetics services due to cost and limited number of genetic centers.…”

Section: Spectrum Of Genetic Disordersmentioning

confidence: 99%

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Medical genetics and genomic medicine in India: current status and opportunities ahead

Aggarwal

Phadke

2015

Molec Gen & Gen Med

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Section: Academic Programs In Medical Geneticsmentioning

confidence: 93%

Section: Spectrum Of Genetic Disordersmentioning

confidence: 99%

Medical genetics and genomic medicine in India: current status and opportunities ahead

Aggarwal

Phadke

2015

Molec Gen & Gen Med

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“…This suggests the lack of founder or common mutations in CFTR gene and thus emphasises the need for sequencing of all coding regions of the CFTR gene in suspected cases in the Indian population. In the present study except for p.Phe508del no other pathogenic variant was present in the ACMG panel of cystic brosis [59]. In view of the heterogeneity in pathogenic variants, Mandal et al also suggested that a single panel of pathogenic variants cannot be used for diagnosis or carrier testing of CF in India [28].…”

Section: Cftr (Cystic Brosis Transmembrane Conductance Regulator) Patmentioning

confidence: 59%

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

Singh¹,

Bijarnia-Mahay²,

Ramprasad

et al. 2020

Preprint

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Background: To determine the carrier frequency and pathogenic variants of common genetic disorders in the north Indian population by using next generation sequencing (NGS).Methods: After pre-test counselling, 200 unrelated individuals (including 88 couples) were screened for pathogenic variants in 88 genes by NGS technology. The variants were classified as per American College of Medical Genetics criteria. Pathogenic and likely pathogenic variants were subjected to thorough literature-based curation in addition to the regular filters. Variants of unknown significance were not reported. Individuals were counselled explaining the implications of the results, and cascade screening was advised when necessary.Results: Of the 200 participants, 52 (26 %) were found to be carrier of one or more disorders. Twelve individuals were identified to be carriers for congenital deafness, giving a carrier frequency of one in 17 for one of the four genes tested (SLC26A4, GJB2, TMPRSS3 and TMC1 in decreasing order). Nine individuals were observed to be carriers for cystic fibrosis, with a frequency of one in 22. Three individuals were detected to be carriers for Pompe disease (frequency one in 67). None of the 88 couples screened were found to be carriers for the same disorder. The pathogenic variants observed in many disorders (such as deafness, cystic fibrosis, Pompe disease, Canavan disease, primary hyperoxaluria, junctional epidermolysis bullosa, galactosemia, medium chain acyl CoA deficiency etc.) were different from those commonly observed in the West. Conclusion: A higher carrier frequency for genetic deafness, cystic fibrosis and Pompe disease was unexpected, and contrary to the generally held view about their prevalence in Asian Indians. In spite of the small sample size, this study would suggest that population-based carrier screening panels for India would differ from those in the West, and need to be selected with due care. Testing should comprise the study of all the coding exons with its boundaries in the genes through NGS, as all the variants are not well characterized. Only study of entire coding regions in the genes will detect carriers with adequate efficiency, in order to reduce the burden of genetic disorders in India and other resource poor countries.

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“…However, it is not predominant mutation in Asian CF patients. Studies from Indian CF patients found low frequency (19-31.1 %,) of del F 508 mutation [9,10]. Another mutation, G551D(or Gly551Asp or Celtic mutation), arises as a consequence of substitution of aspartate residue for a glycine residue at position 551 and accounts for 4 to 5% of alleles [8].…”

Section: Understanding Pathophysiologymentioning

confidence: 99%

Ivacaftor: A Novel Mutation Modulating Drug

Kapoor

Koolwal

Singh

2014

JCDR

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Cystic fibrosis (CF) is multisystemic disorder presenting in newborn period to adulthood, predominantly affecting respiratory system. It is caused by mutation in CF transmembrane conductance regulator gene. ΔF508 is the most common mutation seen worldwide. Supportive management with bronchodilators, anti-inflammatory, mucolytics, antibiotics are the corner stone of therapy. Mutation specific drug, Ivacaftor, was recently approved USFDA in January 2012 for patients carrying G551D mutation. It is approved in patients who are six years and older in 150 mg twice daily dosing schedule with fat containing meals. It improves the lung function and other aspects of disease including weight gain. The side effects like upper respiratory infection, headache, rash, diarrhoea, stomach ache and dizziness are mild and selflimiting. This is excellent example of promise of personalised medicine -targeted drug that treat patients with specific genetic makeup.

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Mutation Analysis of the CFTR Gene in 225 Children: Identification of Five Novel Severe and Seven Reported Severe Mutations

Abstract: The protocol for identification of mutations in cases of CF in developing countries would have to include a different set of mutations than those reported from western countries.

Cited by 16 publications

References 21 publications

Medical genetics and genomic medicine in India: current status and opportunities ahead

Medical genetics and genomic medicine in India: current status and opportunities ahead

NGS based expanded carrier screening for genetic disorders in North Indian population reveals unexpected results – a pilot study.

Ivacaftor: A Novel Mutation Modulating Drug

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