title: A frameshift mutation in HTRA1 expands CARASIL syndrome and peripheral small arterial disease to the Chinese population.
abstract: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary cerebral artery disease. The HtrA serine protease 1 (HTRA1) gene has been identified as the causative gene of CARASIL. Here, we report a novel mutation in the HTRA1 gene in a CARASIL pedigree and explore its pathogenesis at the protein level. Subcutaneous tissue biopsy and HTRA1 gene analysis were performed in a CARASIL patient, and HTRA1 and TGF-β1 protein expression in subcutaneous tissue and cultured fibroblasts from the proband were detected by immunohistochemistry and western blotting. A 28-year-old male proband and his brother experienced recurrent stroke, hair loss and low back pain. Abnormalities in the proband were found in the elastic plate of subcutaneous small arteries, and a novel homozygous frameshift mutation (c.161_162insAG), leading to the formation of a stop codon 159 amino acids downstream of the insertion (p.Gly56Alafs*160) was detected. Reduced HTRA1 protein and increased TGF-β1 expression were detected in subcutaneous tissue and in cultured fibroblasts. A frameshift mutation in the HTRA1 gene detected in a CARASIL pedigree resulted in reduced HTRA1 protein and increased TGF-β1 expression, which may cause severe CARASIL and peripheral small arterial disease.
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, Fujian, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Jiabin
authors.initials: J
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.forename: WenPing
authors.initials: W
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
mesh_terms: D000328:Adult; D000505:Alopecia / Q000235:genetics*; D044466:Asian People; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000235:genetics*; D004252:DNA Mutational Analysis; D005347:Fibroblasts / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics*; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D058729:Peripheral Arterial Disease / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D013122:Spinal Diseases / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases