title: Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism.
abstract: Intellectual disability (ID) is a common disease. While the etiology remains incompletely understood, genetic defects are a major contributor, which include mutations in genes encoding zinc finger proteins. These proteins modulate gene expression via binding to DNA. Consistent with this knowledge, we report here the identification of mutations in the ZNF407 gene in ID/autistic patients. In our study of an ID patient with autism, a reciprocal translocation 46,XY,t(3;18)(p13;q22.3) was detected. By using FISH and long-range PCR approaches, we have precisely mapped the breakpoints associated with this translocation in a gene-free region in chromosome 3 and in the third intron of the ZNF407 gene in chromosome18. The latter reduces ZNF407 expression. Consistent with this observation, in our subsequent investigation of 105 ID/autism patients with similar clinical presentations, two missense mutations Y460C and P1195A were identified. These mutations cause non-conservative amino acid substitutions in the linker regions between individual finger structures. In line with the linker regions being critical for the integrity of zinc finger motifs, both mutations may result in loss of ZNF407 function. Taken together, we demonstrate that mutations in the ZNF407 gene contribute to the pathogenesis of a group of ID patients with autism.
authors.affiliation: Department of Medical Genetics, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Cong-mian
authors.initials: CM
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wei
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Zhang
authors.forename: Shou-qiang
authors.initials: SQ
authors.lastname: Zhong
authors.forename: Heng
authors.initials: H
authors.lastname: Gu
authors.forename: Xing-sheng
authors.initials: XS
authors.lastname: Dong
authors.forename: Yang-yu
authors.initials: YY
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Ke
authors.forename: Xin-ming
authors.initials: XM
authors.lastname: Son
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage; D056905:Chromosome Breakpoints; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C580839:ZNF407 protein, human