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Title: Mosaic uniparental disomy results in GM1 gangliosidosis with normal enzyme assay.
Austin Authors: Myers, Kenneth A;Bennett, Mark F;Chow, Chung W;Carden, Susan M;Mandelstam, Simone A;Bahlo, Melanie;Scheffer, Ingrid E 
Affiliation: Department of Medicine, Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Anatomical Pathology, Royal Children's Hospital, Parkville, Victoria, Australia
Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
The Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Department of Radiology, The University of Melbourne, Parkville, Victoria, Australia
Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia
Issue Date: Jan-2018 2017-11-21
Publication information: American journal of medical genetics. Part A 2018; 176(1): 230-234
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.
DOI: 10.1002/ajmg.a.38549
ORCID: 0000-0001-7831-4593
PubMed URL: 29160035
Type: Journal Article
Subjects: GM1 gangliosidosis
cherry-red spot
ketogenic diet
lysosomal disorders
skin biopsy
uniparental disomy
whole exome sequencing
Appears in Collections:Journal articles

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