title: Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29.
abstract: Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus.
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Yu
authors.affiliation: Division of Quality Management, Shandong Center for Disease Control and Prevention, 16992 Jingshi Road, Jinan 250014, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: You
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Neurology, General Hospital of Jinan Military Region, 25 Shifan Road, Jinan 250031, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Neurology, General Hospital of Jinan Military Region, 25 Shifan Road, Jinan 250031, China.
authors.forename: Chuanfen
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Feng
authors.initials: F
authors.lastname: You
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China. Electronic address: cijnmd@outlook.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.affiliation: Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, 8 Lashan Road, Jinan 250022, China. Electronic address: dwy2115@126.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Duan
mesh_terms: D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
keywords: 3q28–q29; Autosomal recessive; Hereditary spastic paraplegia; Microarray; Neurodegenerative disorder; Run of homozygosity; SPG14