dc.contributor.author |
Whitford, Whitney |
en |
dc.contributor.author |
Hawkins, Isobel |
en |
dc.contributor.author |
Glamuzina, Emma |
en |
dc.contributor.author |
Wilson, Francessa |
en |
dc.contributor.author |
Marshall, Andrew |
en |
dc.contributor.author |
Ashton, Fern |
en |
dc.contributor.author |
Love, Donald |
en |
dc.contributor.author |
Taylor, Juliet |
en |
dc.contributor.author |
Hill, Rosamund |
en |
dc.contributor.author |
Lehnert, Klaus |
en |
dc.contributor.author |
Snell, Russell |
en |
dc.contributor.author |
Jacobsen, Jessie |
en |
dc.date.accessioned |
2018-10-19T02:34:46Z |
en |
dc.date.issued |
2017-11-21 |
en |
dc.identifier.citation |
Cold Spring Harbor Molecular Case Studies 3(6):15 pages Article number a001909 Nov 2017 |
en |
dc.identifier.issn |
2373-2873 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/42976 |
en |
dc.description.abstract |
Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death. Treatment is possible via supplement of biotin and/or thiamine, with early treatment resulting in significant lifelong improvements. Here we report two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5' UTR and minimal promoter region. This deletion is the smallest promoter deletion reported to date, further defining the minimal promoter region of SLC19A3 Unfortunately, one of the siblings died prior to diagnosis, but the other is showing significant improvement after commencement of therapy. This case demonstrates the power of whole-genome sequencing for the identification of structural variants and subsequent diagnosis of rare neurodevelopmental disorders. |
en |
dc.format.medium |
Electronic-Print |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Cold Spring Harbor molecular case studies |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://molecularcasestudies.cshlp.org/site/misc/ifora_policies.xhtml |
en |
dc.rights.uri |
https://creativecommons.org/licenses/by-nc/4.0/ |
en |
dc.subject |
Brain |
en |
dc.subject |
Basal Ganglia |
en |
dc.subject |
Humans |
en |
dc.subject |
Basal Ganglia Diseases |
en |
dc.subject |
Biotin |
en |
dc.subject |
Thiamine |
en |
dc.subject |
Membrane Transport Proteins |
en |
dc.subject |
5' Untranslated Regions |
en |
dc.subject |
Magnetic Resonance Imaging |
en |
dc.subject |
Siblings |
en |
dc.subject |
Mutation |
en |
dc.subject |
Child |
en |
dc.subject |
Female |
en |
dc.subject |
Male |
en |
dc.subject |
Promoter Regions, Genetic |
en |
dc.subject |
Young Adult |
en |
dc.title |
Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1101/mcs.a001909 |
en |
pubs.issue |
6 |
en |
pubs.volume |
3 |
en |
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.pmid |
28696212 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.subtype |
Case Reports |
en |
pubs.elements-id |
637594 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
dc.identifier.eissn |
2373-2873 |
en |
pubs.record-created-at-source-date |
2017-07-12 |
en |
pubs.dimensions-id |
28696212 |
en |