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Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease
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 dysphag...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701311/ https://www.ncbi.nlm.nih.gov/pubmed/28696212 http://dx.doi.org/10.1101/mcs.a001909 |
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author | Whitford, Whitney Hawkins, Isobel Glamuzina, Emma Wilson, Francessa Marshall, Andrew Ashton, Fern Love, Donald R. Taylor, Juliet Hill, Rosamund Lehnert, Klaus Snell, Russell G. Jacobsen, Jessie C. |
author_facet | Whitford, Whitney Hawkins, Isobel Glamuzina, Emma Wilson, Francessa Marshall, Andrew Ashton, Fern Love, Donald R. Taylor, Juliet Hill, Rosamund Lehnert, Klaus Snell, Russell G. Jacobsen, Jessie C. |
author_sort | Whitford, Whitney |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5701311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57013112017-12-04 Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease Whitford, Whitney Hawkins, Isobel Glamuzina, Emma Wilson, Francessa Marshall, Andrew Ashton, Fern Love, Donald R. Taylor, Juliet Hill, Rosamund Lehnert, Klaus Snell, Russell G. Jacobsen, Jessie C. Cold Spring Harb Mol Case Stud Research Report 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. Cold Spring Harbor Laboratory Press 2017-11 /pmc/articles/PMC5701311/ /pubmed/28696212 http://dx.doi.org/10.1101/mcs.a001909 Text en © 2017 Whitford et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Report Whitford, Whitney Hawkins, Isobel Glamuzina, Emma Wilson, Francessa Marshall, Andrew Ashton, Fern Love, Donald R. Taylor, Juliet Hill, Rosamund Lehnert, Klaus Snell, Russell G. Jacobsen, Jessie C. Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title | Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title_full | Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title_fullStr | Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title_full_unstemmed | Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title_short | Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
title_sort | compound heterozygous slc19a3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701311/ https://www.ncbi.nlm.nih.gov/pubmed/28696212 http://dx.doi.org/10.1101/mcs.a001909 |
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