title: A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, choreoathetosis and learning disability.
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.
authors: Hawai'i Community Genetics, Kapi'olani Medical Specialists, Honolulu, Hawaii, United States of America.
authors: Laurie H
authors: LH
authors: Seaver
authors: Xue-Ying
authors: XY
authors: He
authors: Keith
authors: K
authors: Abe
authors: Tina
authors: T
authors: Cowan
authors: Gregory M
authors: GM
authors: Enns
authors: Lawrence
authors: L
authors: Sweetman
authors: Manfred
authors: M
authors: Philipp
authors: Sansan
authors: S
authors: Lee
authors: Mazhar
authors: M
authors: Malik
authors: Song-Yu
authors: SY
authors: Yang
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D001264:Athetosis / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000652:urine; D001483:Base Sequence; D002264:Carboxylic Acids / Q000652:urine; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000652:urine; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004579:Electron Transport; D004827:Epilepsy / Q000150:complications* / Q000201:enzymology / Q000235:genetics* / Q000652:urine; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D007859:Learning Disabilities / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000652:urine; D008297:Male; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy
chemical_list: D002264:Carboxylic Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human