Mosaic uniparental disomy results in GM1 gangliosidosis with normal enzyme assay
- Author(s)
- Myers, KA; Bennett, MF; Chow, CW; Carden, SM; Mandelstam, SA; Bahlo, M; Scheffer, IE;
- Details
- Publication Year 2018-01,Volume 176,Issue #1,Page 230-234
- Journal Title
- Am J Med Genet A
- Publication Type
- Journal Article
- Abstract
- Inherited metabolic disorders are traditionally diagnosed using broad and expensive panels of screening tests, often including invasive skin and muscle biopsy. Proponents of next-generation genetic sequencing have argued that replacing these screening panels with whole exome sequencing (WES) would save money. Here, we present a complex patient in whom WES allowed diagnosis of GM1 gangliosidosis, caused by homozygous GLB1 mutations, resulting in beta-galactosidase deficiency. A 10-year-old girl had progressive neurologic deterioration, macular cherry-red spot, and cornea verticillata. She had marked clinical improvement with initiation of the ketogenic diet. Comparative genomic hybridization microarray showed mosaic chromosome 3 paternal uniparental disomy (UPD). GM1 gangliosidosis was suspected, however beta-galactosidase assay was normal. Trio WES identified a paternally-inherited pathogenic splice-site GLB1 mutation (c.75+2dupT). The girl had GM1 gangliosidosis; however, enzymatic testing in blood was normal, presumably compensated for by non-UPD cells. Severe neurologic dysfunction occurred due to disruptive effects of UPD brain cells.
- Publisher
- Wiley
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 29160035
- Publisher's Version
- https://doi.org/10.1002/ajmg.a.38549
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-01-15 09:30:01
Last Modified: 2018-02-14 03:50:11