TY - JOUR
T1 - Recurrent and novel GLB1 mutations in India
AU - Bidchol, Abdul Mueed
AU - Dalal, Ashwin
AU - Trivedi, Rakesh
AU - Shukla, Anju
AU - Nampoothiri, Sheela
AU - Sankar, V. H.
AU - Danda, Sumita
AU - Gupta, Neerja
AU - Kabra, Madhulika
AU - Hebbar, Shrikiran A.
AU - Bhat, Ramesh Y.
AU - Matta, Divya
AU - Ekbote, Alka V.
AU - Puri, Ratna Dua
AU - Phadke, Shubha R.
AU - Gowrishankar, Kalpana
AU - Aggarwal, Shagun
AU - Ranganath, Prajnya
AU - Sharda, Sheetal
AU - Kamate, Mahesh
AU - Datar, Chaitanya A.
AU - Bhat, Kamalakshi
AU - Kamath, Nutan
AU - Shah, Hitesh
AU - Krishna, Shuba
AU - Gopinath, Puthiya Mundyat
AU - Verma, Ishwar C.
AU - Nagarajaram, H. A.
AU - Satyamoorthy, Kapaettu
AU - Girisha, Katta Mohan
PY - 2015/8/10
Y1 - 2015/8/10
N2 - GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-. d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.
AB - GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-. d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.
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U2 - 10.1016/j.gene.2015.04.078
DO - 10.1016/j.gene.2015.04.078
M3 - Article
C2 - 25936995
AN - SCOPUS:84938926694
SN - 0378-1119
VL - 567
SP - 173
EP - 181
JO - Gene
JF - Gene
IS - 2
ER -