{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T18:52:12Z","timestamp":1769280732861,"version":"3.49.0"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1091593"],"award-info":[{"award-number":["1091593"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1104831"],"award-info":[{"award-number":["1104831"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Inherited metabolic disorders are traditionally diagnosed using broad and expensive panels of screening tests, often including invasive skin and muscle biopsy. Proponents of next\u2010generation 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 <jats:italic>GLB1<\/jats:italic> mutations, resulting in \u03b2\u2010galactosidase deficiency. A 10\u2010year\u2010old girl had progressive neurologic deterioration, macular cherry\u2010red 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 \u03b2\u2010galactosidase assay was normal. Trio WES identified a paternally\u2010inherited pathogenic splice\u2010site <jats:italic>GLB1<\/jats:italic> mutation (c.75+2dupT). The girl had GM1 gangliosidosis; however, enzymatic testing in blood was normal, presumably compensated for by non\u2010UPD cells. Severe neurologic dysfunction occurred due to disruptive effects of UPD brain cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38549","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T05:43:07Z","timestamp":1511242987000},"page":"230-234","source":"Crossref","is-referenced-by-count":5,"title":["Mosaic uniparental disomy results in GM1 gangliosidosis with normal enzyme assay"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7831-4593","authenticated-orcid":false,"given":"Kenneth A.","family":"Myers","sequence":"first","affiliation":[{"name":"Department of Medicine Epilepsy Research Centre The University of Melbourne, Austin Health Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark F.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Medicine Epilepsy Research Centre The University of Melbourne, Austin Health Heidelberg Victoria Australia"},{"name":"The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia"},{"name":"Department of Medical Biology The University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung W.","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Royal Children's Hospital Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne Royal Children's Hospital Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"Carden","sequence":"additional","affiliation":[{"name":"Department of Paediatrics The University of Melbourne Royal Children's Hospital Parkville Victoria Australia"},{"name":"The Royal Victorian Eye and Ear Hospital East Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone A.","family":"Mandelstam","sequence":"additional","affiliation":[{"name":"Department of Paediatrics The University of Melbourne Royal Children's Hospital Parkville Victoria Australia"},{"name":"Department of Radiology The University of Melbourne Parkville Victoria Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Bahlo","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia"},{"name":"Department of Medical Biology The University of Melbourne Parkville Victoria Australia"},{"name":"Department of Mathematics and Statistics The University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Medicine Epilepsy Research Centre The University of Melbourne, Austin Health Heidelberg Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne Royal Children's Hospital Parkville Victoria Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.03.018"},{"issue":"6","key":"e_1_2_6_3_1","first-page":"1004","article-title":"Mutations in the lysosomal beta\u2010galactosidase gene that cause the adult form of GM1 gangliosidosis","volume":"54","author":"Chakraborty S.","year":"1994","journal-title":"American Journal of Human Genetics"},{"issue":"2","key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1001\/archopht.1971.00990050179011","article-title":"GM1\u2010gangliosidosis. 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