Mutation Studies in theCFTRGene in Asian Indian Subjects with Congenital Bilateral Absence of Vas Deferens: Report of Two Novel Mutations and Four Novel Variants

Abstract

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

The CFTR gene mild variants poly-T, TG repeats and M470V detection in Indian men with congenital bilateral absence of vas deferens

“…Notably, we found the c.1210‐12T[5] allele to be significantly higher in the cohort of CBAVD men (39.4%) as compared to the healthy men. Our observations fall in the range 28 ‐54% reported in other Indian studies (Sachdeva et al., ; Sharma, Acharyam, et al., ). It was higher than those reported in Italian (8.3%) (Pradal, Castellani, Delmarco, & Mastella, ), Iranian (10%) (Radpour, Gourabi, Gilani, & Dizaj, ), Argentinian (11%) (Levy et al., ), German (12.3%) (Dörk et al., ), American (17.9%) (Wang et al., ), Taiwanese (19.4%) (Wu et al., ), French (16.3%) (Claustres et al., ), Portuguese (27.4%) (Grangeia et al., ) and Egyptian (28.6%) Fathy et al.…”

“…Strong linkage disequilibrium is evident among c.1210‐12T [5] and the Val allele of M470V polymorphism in CBAVD but not in general population (de Meeus et al., ). Studies in population from North India reported 25‐56% frequency of IVS‐9‐ c.1210‐12T [5] (Sachdeva, Saxena, Majumdar, Chadha, & Verma, ; Sharma, Singh, Kaur, Thapa, & Prasad, ; Sharma, Acharyam, et al., ). The ethnicity of the Indian population is quite heterogeneous with different geographical distribution.…”

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

“…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.…”

“…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.…”

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

“…CFTR c.3854C>T, p.Ala1285Val variant was identi ed in three individuals, which though has been reported in the literature [55] associated with congenital bilateral absence of vas deferens CBAVD), is more likely to represent a common polymorphism due to its observance in high frequency in the NGS data in the Indian population (0.5% minor allele frequency in South Asians in gnomAD exomes). This variant was classi ed as VUS and not included in the list of disease associated variants.…”