title: 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).
abstract: 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.
  
  
  CONCLUSIONS
  Discovery of a novel missense mutation (c.854C>T) associated with CARASIL expands the known CARASIL-related mutations in HTRA1.
authors: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors: Yan
authors: Y
authors: Chen
authors: Zhiyi
authors: Z
authors: He
authors: Su
authors: S
authors: Meng
authors: Lei
authors: L
authors: Li
authors: Hua
authors: H
authors: Yang
authors: Xiaotang
authors: X
authors: Zhang
mesh_terms: D000328:Adult; D000505:Alopecia / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D019943:Amino Acid Substitution; D044466:Asian People; D001483:Base Sequence; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D005190:Family; D005260:Female; D006579:Heterozygote; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006720:Homozygote; D006801:Humans; D006860:Hydrogen Bonding; D056784:Leukoencephalopathies / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013122:Spinal Diseases / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases
keywords: CARASIL; HTRA1; cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; high-temperature requirement A serine peptidase 1; mutation