Recurrent and novel GLB1 mutations in India

Abdul Mueed Bidchol, Ashwin Dalal, Rakesh Trivedi, Anju Shukla, Sheela Nampoothiri, V. H. Sankar, Sumita Danda, Neerja Gupta, Madhulika Kabra, Shrikiran A. Hebbar, Ramesh Y. Bhat, Divya Matta, Alka V. Ekbote, Ratna Dua Puri, Shubha R. Phadke, Kalpana Gowrishankar, Shagun Aggarwal, Prajnya Ranganath, Sheetal Sharda, Mahesh KamateChaitanya A. Datar, Kamalakshi Bhat, Nutan Kamath, Hitesh Shah, Shuba Krishna, Puthiya Mundyat Gopinath, Ishwar C. Verma, H. A. Nagarajaram, Kapaettu Satyamoorthy, Katta Mohan Girisha

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalGene
Volume567
Issue number2
DOIs
Publication statusPublished - 10-08-2015

Fingerprint

India
Mutation
GM1 Gangliosidosis
Galactosidases
Nonsense Codon
Gene Frequency
Computer Simulation
Genes
Sequence Analysis
Exons
Enzymes
Population
Proteins

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Genetics

Cite this

Bidchol, A. M., Dalal, A., Trivedi, R., Shukla, A., Nampoothiri, S., Sankar, V. H., ... Girisha, K. M. (2015). Recurrent and novel GLB1 mutations in India. Gene, 567(2), 173-181. https://doi.org/10.1016/j.gene.2015.04.078
Bidchol, Abdul Mueed ; Dalal, Ashwin ; Trivedi, Rakesh ; Shukla, Anju ; Nampoothiri, Sheela ; Sankar, V. H. ; Danda, Sumita ; Gupta, Neerja ; Kabra, Madhulika ; Hebbar, Shrikiran A. ; Bhat, Ramesh Y. ; Matta, Divya ; Ekbote, Alka V. ; Puri, Ratna Dua ; Phadke, Shubha R. ; Gowrishankar, Kalpana ; Aggarwal, Shagun ; Ranganath, Prajnya ; Sharda, Sheetal ; Kamate, Mahesh ; Datar, Chaitanya A. ; Bhat, Kamalakshi ; Kamath, Nutan ; Shah, Hitesh ; Krishna, Shuba ; Gopinath, Puthiya Mundyat ; Verma, Ishwar C. ; Nagarajaram, H. A. ; Satyamoorthy, Kapaettu ; Girisha, Katta Mohan. / Recurrent and novel GLB1 mutations in India. In: Gene. 2015 ; Vol. 567, No. 2. pp. 173-181.
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abstract = "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.",
author = "Bidchol, {Abdul Mueed} and Ashwin Dalal and Rakesh Trivedi and Anju Shukla and Sheela Nampoothiri and Sankar, {V. H.} and Sumita Danda and Neerja Gupta and Madhulika Kabra and Hebbar, {Shrikiran A.} and Bhat, {Ramesh Y.} and Divya Matta and Ekbote, {Alka V.} and Puri, {Ratna Dua} and Phadke, {Shubha R.} and Kalpana Gowrishankar and Shagun Aggarwal and Prajnya Ranganath and Sheetal Sharda and Mahesh Kamate and Datar, {Chaitanya A.} and Kamalakshi Bhat and Nutan Kamath and Hitesh Shah and Shuba Krishna and Gopinath, {Puthiya Mundyat} and Verma, {Ishwar C.} and Nagarajaram, {H. A.} and Kapaettu Satyamoorthy and Girisha, {Katta Mohan}",
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Bidchol, AM, Dalal, A, Trivedi, R, Shukla, A, Nampoothiri, S, Sankar, VH, Danda, S, Gupta, N, Kabra, M, Hebbar, SA, Bhat, RY, Matta, D, Ekbote, AV, Puri, RD, Phadke, SR, Gowrishankar, K, Aggarwal, S, Ranganath, P, Sharda, S, Kamate, M, Datar, CA, Bhat, K, Kamath, N, Shah, H, Krishna, S, Gopinath, PM, Verma, IC, Nagarajaram, HA, Satyamoorthy, K & Girisha, KM 2015, 'Recurrent and novel GLB1 mutations in India', Gene, vol. 567, no. 2, pp. 173-181. https://doi.org/10.1016/j.gene.2015.04.078

Recurrent and novel GLB1 mutations in India. / Bidchol, Abdul Mueed; Dalal, Ashwin; Trivedi, Rakesh; Shukla, Anju; Nampoothiri, Sheela; Sankar, V. H.; Danda, Sumita; Gupta, Neerja; Kabra, Madhulika; Hebbar, Shrikiran A.; Bhat, Ramesh Y.; Matta, Divya; Ekbote, Alka V.; Puri, Ratna Dua; Phadke, Shubha R.; Gowrishankar, Kalpana; Aggarwal, Shagun; Ranganath, Prajnya; Sharda, Sheetal; Kamate, Mahesh; Datar, Chaitanya A.; Bhat, Kamalakshi; Kamath, Nutan; Shah, Hitesh; Krishna, Shuba; Gopinath, Puthiya Mundyat; Verma, Ishwar C.; Nagarajaram, H. A.; Satyamoorthy, Kapaettu; Girisha, Katta Mohan.

In: Gene, Vol. 567, No. 2, 10.08.2015, p. 173-181.

Research output: Contribution to journalArticle

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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Bidchol AM, Dalal A, Trivedi R, Shukla A, Nampoothiri S, Sankar VH et al. Recurrent and novel GLB1 mutations in India. Gene. 2015 Aug 10;567(2):173-181. https://doi.org/10.1016/j.gene.2015.04.078