title: Identification of RELN variation p.Thr3192Ser in a Chinese family with schizophrenia.
abstract: Schizophrenia (SCZ) is a serious psychiatric disease with strong heritability. Its complexity is reflected by extensive genetic heterogeneity and much of the genetic liability remains unaccounted for. We applied a combined strategy involving detection of copy number variants (CNVs), whole-genome mapping, and exome sequencing to identify the genetic basis of autosomal-dominant SCZ in a Chinese family. To rule out pathogenic CNVs, we first performed Illumina single nucleotide polymorphism (SNP) array analysis on samples from two patients and one psychiatrically healthy family member, but no pathogenic CNVs were detected. In order to further narrow down the susceptible region, we conducted genome-wide linkage analysis and mapped the disease locus to chromosome 7q21.13-22.3, with a maximum multipoint logarithm of odds score of 2.144. Whole-exome sequencing was then carried out with samples from three affected individuals and one unaffected individual in the family. A missense variation c.9575 C > G (p.Thr3192Ser) was identified in RELN, which is known as a risk gene for SCZ, located on chromosome 7q22, in the pedigree. This rare variant, as a highly penetrant risk variant, co-segregated with the phenotype. Our results provide genetic evidence that RELN may be one of pathogenic gene in SCZ.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Genetics, Changsha 410008, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: BGI-Shenzhen, Shenzhen, Guangdong Province, 518083, China.|Department of Computer Science, City University of Hong Kong, Hong Kong 999077, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Mental Health Centre, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Zhening
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Mental Health Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medical Genetics, Changsha 410008, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.|State Key Laboratory of Medical Genetics, Changsha 410008, China.
authors.forename: Bengsha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.|State Key Laboratory of Medical Genetics, Changsha 410008, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002681:China; D056915:DNA Copy Number Variations; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D000091042:Reelin Protein; D012559:Schizophrenia / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases