2012 Fiscal Year Final Research Report

Molecular mechanism for a cerebral small vessel disease caused by heterozygosity for novel mutations in HTRA1 gene

Research Project

Project/Area Number	23790983
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Neurology
Research Institution	Niigata University
Principal Investigator	NOZAKI Hiroaki 新潟大学, 医歯学系, 助教 (20547567)
Project Period (FY)	2011 – 2012
Keywords	HTRA1 / CARASIL / cerebral small vessel disease / dominant negative
Research Abstract	Homozygous mutations in the high temperature requirement serine peptidase A1 (HTRA1) gene cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) by decrease of its protease activity. We analyzed HTRA1 ORF sequences in 41 patients with CARASIL-like syndrome 〓70 years of age carrying no notch3 mutations and found 4 patients (9.8%) carrying heterozygous novel mutations in the HTRA1 gene. Although two nonsense mutations in the HTRA1 gene, which result in null expression, have been reported in CARASIL patients, no one carrying the heterozygous nonsense mutation presented CARASIL-like syndrome. In this study, we elucidated inhibitory effect of novel mutated HTRA1s on protease activity of wild type HTRA1.

(4 results)