Expanding the spectrum of HEXA mutations in Indian patients with Tay–Sachs disease
| Autor: | Sheela Nampoothiri, Shekhar Patil, Mehul Mistri, Jayesh Sheth, Chaitanya Datar, Frenny Sheth, Harshuti Shah, Sarita Gupta, Mahesh Kamate, Umesh Kalane |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
HEXA gene
TSD Tay–Sachs disease Nonsense mutation Population Biology Compound heterozygosity Exon Endocrinology Genetics medicine Missense mutation education lcsh:QH301-705.5 Molecular Biology MUGS 4-Methylumbelliferyl-N-acetyl-β-d-glucosamine-6-sulfate lcsh:R5-920 education.field_of_study Splice site mutation SD Sandhoff disease MUG 4-Methylumbelliferyl-N-acetyl-β-d-glucosamine Tay-Sachs disease Tay–Sachs disease HEXA medicine.disease Lysosomal enzyme The Lysosome lcsh:Biology (General) β-Hexosaminidase-A Hex-A β-Hexosaminidase A LSDs Lysosomal storage disorders lcsh:Medicine (General) |
| Zdroj: | Molecular Genetics and Metabolism Reports Molecular Genetics and Metabolism Reports, Vol 1, Iss C, Pp 425-430 (2014) |
| ISSN: | 2214-4269 |
| Popis: | Tay–Sachs disease is an autosomal recessive neurodegenerative disorder occurring due to impaired activity of β-hexosaminidase-A (EC 3.2.1.52), resulting from the mutation in HEXA gene. Very little is known about the molecular pathology of TSD in Indian children except for a few mutations identified by us. The present study is aimed to determine additional mutations leading to Tay–Sachs disease in nine patients confirmed by the deficiency of β-hexosaminidase-A (C (D175A) and c.805G>C (p.G269R) in one case; and one small 1 bp deletion c.426delT (p.F142LfsX57) and one splice site mutation c.459+4A>C in the other two cases respectively. None of these mutations were detected in 100 chromosomes from healthy individuals of the same ethnic group. Three previously reported missense mutations, (i) c.532C>T (p.R178C), (ii) c.964G>T (p.D322Y), and (iii) c.1385A>T (p.E462V); two nonsense mutations (i) c.709C>T (p.Q237X) and (ii) c.1528C>T (p.R510X), one 4 bp insertion c.1277_1278insTATC (p.Y427IfsX5) and one splice site mutation c.459+5G>A were also identified in six cases. We observe from this study that novel mutations are more frequently observed in Indian patients with Tay–Sachs disease with clustering of ~ 73% of disease causing mutations in exons 5 to 12. This database can be used for a carrier rate screening in the larger population of the country. |
| Databáze: | OpenAIRE |
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