Journal of Genetic Counseling

, Volume 23, Issue 5, pp 734–741 | Cite as

Maternal Uniparental Isodisomy Causing Autosomal Recessive GM1 Gangliosidosis: A Clinical Report

  • Jessica E. King
  • Amy Dexter
  • Inder Gadi
  • Val Zvereff
  • Meaghan Martin
  • Miriam Bloom
  • Adeline VanderverEmail author
  • Amy Pizzino
  • Johanna L. Schmidt
Case Presentation


Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase. Subsequently, homozygous missense mutations in the galactosidase, beta 1 (GLB1) gene on chromosome 3 were found. Parental testing confirmed inheritance of two copies of the same mutated maternal GLB1 gene, and no paternal copy. SNP analysis was also done to confirm paternity. The patient was ultimately diagnosed with autosomal recessive GM1 gangliosidosis caused by maternal uniparental isodisomy. We provide a review of this patient and others in which uniparental disomy (UPD) of a non-imprinted chromosome unexpectedly caused an autosomal recessive condition. This is the first case of GM1 gangliosidosis reported in the literature to have been caused by UPD. It is important for genetic counselors and other health care providers to be aware of the possibility of autosomal recessive disease caused by UPD. UPD as a cause of autosomal recessive disease drastically changes the recurrence risk for families, and discussions surrounding UPD can be complex. Working with families to understand UPD when it occurs requires a secure and trusting counselor-family relationship.


Autosomal recessive Uniparental disomy Isodisomy GM1 gangliosidosis GLB1 



We acknowledge the family who provided clinical information as part of the Myelin Disorders Bioregistry Project. We also acknowledge the support of the Delman fund in support of JK, and the Department of Neurology at Children’s National Medical Center.

Conflict of Interest

Authors Jessica E. King, Amy Dexter, Inder Gadi, Val Zvereff, Meaghan Martin, Miriam Bloom, Adeline Vanderver, Amy Pizzino, and Johanna L. Schmidt declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients being included in this study.

Human and Animal Rights

No animal or human studies were carried out by the authors for this article.


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Copyright information

© National Society of Genetic Counselors, Inc. 2014

Authors and Affiliations

  • Jessica E. King
    • 1
  • Amy Dexter
    • 2
  • Inder Gadi
    • 2
  • Val Zvereff
    • 2
  • Meaghan Martin
    • 2
  • Miriam Bloom
    • 1
  • Adeline Vanderver
    • 1
    Email author
  • Amy Pizzino
    • 1
  • Johanna L. Schmidt
    • 1
  1. 1.Department of NeurologyChildren’s National Medical CenterWashingtonUSA
  2. 2.Laboratory Corporation of AmericaResearch Triangle ParkUSA

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