Austin Health

Title
Mosaic uniparental disomy results in GM1 gangliosidosis with normal enzyme assay.
Publication Date
2018-01
Author(s)
Myers, Kenneth A
Bennett, Mark F
Chow, Chung W
Carden, Susan M
Mandelstam, Simone A
Bahlo, Melanie
Scheffer, Ingrid E
Subject
GM1 gangliosidosis
cherry-red spot
ketogenic diet
lysosomal disorders
mosaic
skin biopsy
uniparental disomy
whole exome sequencing
Type of document
Journal Article
OrcId
0000-0001-7831-4593
0000-0002-2311-2174
DOI
10.1002/ajmg.a.38549
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 β-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 β-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.
Link
Citation
American journal of medical genetics. Part A 2018; 176(1): 230-234
Jornal Title
American journal of medical genetics. Part A

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