Functional analysis of HSD 10 disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16245
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Sasai Hideo 岐阜大学, 医学部附属病院, 助教 (20509781)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: HSD10病 / 先天代謝異常症 / ケトン体

Outline of Final Research Achievements

HSD10 disease is a rare X-linked recessive disorders caused by a mutation in the HSD17B10 gene. HSD10 is a multifunctional protein which has three functions. Clinical severity of this disorder is various ranging neonatal severe form to atypical form. The HSD17B10 gene was incorporated into pET28a and the vectors with wild-type cDNA or with each mutant cDNA (A154T, A157V, R226Q) were used to produce high-purity recombinant protein in E. coli expression system. The enzyme activity of 2M3HBD in the isoleucine metabolism system was measured spectrophotometrically. The enzyme activity of 2M3HBD in the mutant protein was significantly decreased compared to wild-type. Also, as compared with A154T and A157V, the enzyme activity was lower in R226Q. In this experiment, there is a certain correlation between the decrease in activity of 2M3HBD and the clinical severity in the isoleucine metabolism system. We are planning to study the further functional analysis.

Free Research Field

先天代謝異常症

Academic Significance and Societal Importance of the Research Achievements

申請者らはこれまで、ケトン体代謝異常症の遺伝子解析を行ってきた。そして、国内初のHSD10病の幼児例を含む本症3症例を明らかにしており、国内での解析は申請者らが中心であり独創的であるといえる。HSD10病の詳しい病態や長期予後は分かっておらず、本研究の結果は国内外問わず学術的にも臨床的にも大きな意味があるものと考える。