Solmaz Jamali1, Nasim Eskandari2, Omid Aryani2, Shadab Salehpour3, Talieh Zaman4, Behnam Kamalidehghan5, Massoud Houshmand6. 1. Dept. of Genetics, Islamic Azad University, Ahar, Iran. 2. Dept. of Genetics, Special Medical Center, Tehran, Iran. 3. Dept. of Pediatrics, Mofid Children's Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. 4. Dept. of Pediatric Metabolic Disorders, Tehran University of Medical Sciences, Tehran, Iran. 5. Dept. of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. 6. National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Abstract
BACKGROUND: Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. METHODS: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. RESULTS: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. CONCLUSION: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations.
BACKGROUND:Tay-Sachs disease (TSD), or GM2 gangliosidosis, is a lethal autosomal recessive neurodegenerative disorder, which is caused by a deficiency of beta-hexosaminidase A (HEXA), resulting in lysosomal accumulation of GM2 ganglioside. The aim of this study was to identify the TSD-causing mutations in an Iranian population. METHODS: In this study, we examined 31 patients for TSD-causing mutations using PCR, followed by restriction enzyme digestion. RESULTS: Molecular genetics analysis of DNA from 23 patients of TSD revealed mutations that has been previously reported, including four-base duplications c.1274_1277dupTATC in exon 11 and IVS2+1G>A, deletion TTAGGCAAGGGC in exon 10 as well as a few novel mutations, including C331G, which altered Gln>Glu in HEXB, A>G, T>C, and p.R510X in exon 14, which predicted a termination codon or nonsense mutation. CONCLUSION: In conclusion, with the discovery of these novel mutations, the genotypic spectrum of Iranian patients with TSD disease has been extended and could facilitate definition of disease-related mutations.
Entities:
Keywords:
Tay-Sachs disease; β- hexosaminidase A; β- hexosaminidase B
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