A novel mutation of the high-temperature requirement A serine peptidase 1 (HTRA1) gene in a Chinese family with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

作者：Chen, Yan; He, Zhiyi^*; Meng, Su; Li, Lei; Yang, Hua; Zhang, Xiaotang

来源：Journal of International Medical Research, 2013, 41(5): 1445-1455.

DOI：10.1177/0300060513480926

• CARASIL
• cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
• high-temperature requirement A serine peptidase 1
• HTRA1
• mutation

Objective: Mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene were studied in a Chinese family with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Methods: Exons 1-9 of the HTRA1 gene were amplified and bidirectionally sequenced in a Chinese family with CARASIL. Mutation effects were analysed by three-dimensional modelling of the serine protease HTRA1 protein. Results: The proband was found to be homozygous for a novel missense mutation (c.854 C>T) identified in exon 4 of the HTRA1 gene; the parents of the proband were heterozygous for the same missense mutation. This c.854 C>T mutation resulted in a change from proline to leucine (p.P285L) in serine protease HTRA1, and was absent in 260 control chromosomes. Three-dimensional models showed that the change from proline to leucine (p.P285L) could attenuate the hydrogen bond between S284 and S287 residues, which might affect function of serine protease HTRA1. Conclusion: Discovery of a novel missense mutation (c.854C>T) associated with CARASIL expands the known CARASIL-related mutations in HTRA1.

• 出版日期2013-10
• 单位中国医科大学