Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India

BMC Med Genet. 2018 Jul 4;19(1):109. doi: 10.1186/s12881-018-0632-7.

Abstract

Background: Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion.

Methods: Multiplex Ligation-dependent Probe Amplification (MLPA) study was carried out in 5 unrelated patients for copy number changes where heterozygous and/or homozygous disease causing mutation/s could not be identified in the coding region by sequencing of HEXA gene.

Results: The study has identified the presence of a homozygous deletion of exon-2 and exon-3 in two patients, two patient showed compound heterozygosity with exon 1 deletion combined with missense mutation p.E462V and one patient was identified with duplication of exon-1 with novel variants c.1527-2A > T as a second allele.

Conclusion: This is the first report of deletion/duplication in HEXA gene providing a new insight into the molecular basis of TSD and use of MLPA assay for detecting large copy number changes in the HEXA gene.

Keywords: HEXA gene; MLPA; Tay-Sachs disease; ß-hexosaminidase-A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons / genetics
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • India
  • Infant
  • Male
  • Mutation, Missense / genetics
  • Sequence Deletion / genetics*
  • Tay-Sachs Disease / genetics*
  • beta-Hexosaminidase alpha Chain / genetics*

Substances

  • HEXA protein, human
  • beta-Hexosaminidase alpha Chain