Tay Sachs disease (TSD) (MIM# 272800) is an autosomal recessive neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutation in the HEXA gene (MIM* 606869) encoding the α subunit of hexosaminidase A, a lysosomal enzyme composed of α and β polypeptides. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. The work at Genetic Research Center, NIRRH (National Institute for Research in Reproductive Health) was supported by intramural funds. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: The work at FRIGE was supported by grant from Indian council of medical research (ICMR), project no BMS: 54/2010. Received: OctoAccepted: Published: June 18, 2012Ĭopyright: © 2012 Mistri et al. PLoS ONE 7(6):Įditor: Markus Schuelke, Charité Universitätsmedizin Berlin, NeuroCure Clinical Research Center, Germany (2012) Identification of Novel Mutations in HEXA Gene in Children Affected with Tay Sachs Disease from India. We conclude that TSD patients from Gujarat should be screened for the common mutation p.E462V.Ĭitation: Mistri M, Tamhankar PM, Sheth F, Sanghavi D, Kondurkar P, Patil S, et al. Mutations could not be identified in one family. A previously known splice site mutation c.805+1 G>C and another intronic mutation c.672+30 T>G of unknown significance were also identified. The mutation p.E462V was found in six unrelated families from Gujarat indicating a founder effect. Fifteen families were included in the study. In silico analysis for mutations was carried out using SIFT, Polyphen2, and Accelrys Discovery Studio softwares. Mutations were confirmed in parents and looked up in public databases. The exons and exon-intron boundaries of the HEXA gene were bidirectionally sequenced using an automated sequencer. Total leukocyte hexosaminidase activity was assayed by 4-methylumbelliferyl-N-acetyl-β-D-glucosamine lysis and hexosaminidase A activity was assayed by heat inactivation method and 4-methylumbelliferyl-N-acetyl-β-D-glucosamine-6-sulphate lysis method. Biochemical criteria included deficiency of hexosaminidase A (less than 2% of total hexosaminidase activity for infantile patients). Neuroimaging criteria included thalamic hyperdensities on CT scan/T1W images of MRI of the brain. The clinical inclusion criteria included neuroregression, seizures, exaggerated startle reflex, macrocephaly, cherry red spot on fundus examination and spasticity. We aimed to determine mutations leading to TSD in India by complete sequencing of the HEXA gene. The mutations leading to Tay Sachs disease in India are yet unknown. Tay Sachs disease (TSD) is a neurodegenerative disorder due to β-hexosaminidase A deficiency caused by mutations in the HEXA gene.
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