Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI115863

An unusual splicing mutation in the HEXB gene is associated with dramatically different phenotypes in patients from different racial backgrounds.

B McInnes, M Potier, N Wakamatsu, S B Melancon, M H Klavins, S Tsuji, and D J Mahuran

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by McInnes, B. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Potier, M. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Wakamatsu, N. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Melancon, S. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Klavins, M. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Tsuji, S. in: PubMed | Google Scholar

Research Institute, Hospital for Sick Children, Montréal, Québec, Canada.

Find articles by Mahuran, D. in: PubMed | Google Scholar

Published August 1, 1992 - More info

Published in Volume 90, Issue 2 on August 1, 1992
J Clin Invest. 1992;90(2):306–314. https://doi.org/10.1172/JCI115863.
© 1992 The American Society for Clinical Investigation
Published August 1, 1992 - Version history
View PDF
Abstract

Sandhoff disease is caused by mutations affecting the beta subunit of lysosomal beta-hexosaminidase (EC 3.2.1.52) and displays a wide spectrum of clinical phenotypes. We report a 57-year-old patient with a very mild phenotype, although residual hexosaminidase A activity in his cultured fibroblasts was less than 3% of normal activity, a level observed in juvenile onset patients. Northern and Western blot analyses confirmed a similar low level of beta subunit-mRNA and mature beta-protein, respectively. Two mutations of the HEXB gene were identified in this patient, a partial 5' gene deletion (a null allele), and a C----T transition 8 nucleotides downstream from the intron 10/exon 11 junction affecting the splicing of the beta subunit-mRNA. In their homozygous forms, the 5' deletion has been previously shown to result in a severe infantile phenotype, and the C----T transition in a juvenile phenotype. The genotype and the low level of residual hexosaminidase A activity would be expected to produce a juvenile Sandhoff phenotype in this patient, as well as in four of his six clinically normal siblings. The biochemical basis of his mild phenotype is uncertain, but may result from genetic variations in the RNA splicing machinery.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 306
page 306
icon of scanned page 307
page 307
icon of scanned page 308
page 308
icon of scanned page 309
page 309
icon of scanned page 310
page 310
icon of scanned page 311
page 311
icon of scanned page 312
page 312
icon of scanned page 313
page 313
icon of scanned page 314
page 314
Version history
  • Version 1 (August 1, 1992): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts