Recurrent and novel GLB1 mutations in India.
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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
Recurrent and novel GLB1 mutations in India.
Gene. 2015 Aug 10;567(2):173-81. doi: 10.1016/j.gene.2015.04.078. Epub 2015 Apr 30.
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- 25936995 [ View in PubMed]
- Abstract
GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme beta-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, beta-domain 1 and beta-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.