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A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (11), pp. e27348. Date of Electronic Publication: 2011 Nov 22. - Publication Year :
- 2011
-
Abstract
- Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this gene result in HSD10 deficiency, whereas a silent mutation results in mental retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense mutation found in the HSD17B10 gene, namely c.194T>C transition (rs104886492), brought about by the loss of two forked methyl groups of valine 65 in the HSD10 active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a neurological syndrome with metabolic derangements, choreoathetosis, refractory epilepsy and learning disability. He has no history of acute decompensation or metabolic acidosis whereas his urine organic acid profile, showing elevated levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of HSD10 deficiency. His HSD10 activity was much lower than the normal control level, with normal β-ketothiolase activity. The c.194T>C mutation in HSD17B10 can be identified by the restriction fragment polymorphism analysis, thereby facilitating the screening of this novel mutation in individuals with intellectual disability of unknown etiology and their family members much easier. The patient's mother is an asymptomatic carrier, and has a mixed ancestry (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency patients are not confined to a particular ethnicity although previously reported cases were either Spanish or German descendants.
- Subjects :
- 3-Hydroxyacyl CoA Dehydrogenases chemistry
Adult
Amino Acid Sequence
Athetosis enzymology
Athetosis genetics
Athetosis urine
Base Sequence
Carboxylic Acids urine
Child
Child, Preschool
Chorea enzymology
Chorea genetics
Chorea urine
DNA Mutational Analysis
Electroencephalography
Electron Transport
Epilepsy enzymology
Epilepsy urine
Female
Fibroblasts enzymology
Humans
Infant, Newborn
Learning Disabilities enzymology
Learning Disabilities genetics
Learning Disabilities urine
Male
Metabolic Networks and Pathways
Mitochondria enzymology
Molecular Sequence Data
Polymorphism, Restriction Fragment Length
Pregnancy
3-Hydroxyacyl CoA Dehydrogenases genetics
Athetosis complications
Chorea complications
Epilepsy complications
Epilepsy genetics
Learning Disabilities complications
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22132097
- Full Text :
- https://doi.org/10.1371/journal.pone.0027348