title: Exome sequencing identifies a de novo mutation in HDAC8 associated with Cornelia de Lange syndrome.
abstract: Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous developmental disorder. The clinical features of CdLS include growth retardation, intellectual disability, limb defects, typical facial dysmorphism and other systemic involvement. Here, we present the clinical and genetic characterization of a sporadic CdLS trio. The proband is a 7-year-old girl with typical CdLS, and both parents are apparently healthy. Whole-exome sequencing of the patient and of both her unaffected parents revealed a previously unobserved de novo mutation in exon 6 of the HDAC8 gene (chrX: 71684483, c.586 A>T; p.M196K). Thus, we have further founded that the p.M196K mutation in HDAC8 is a relevant causal mutation for CdLS.
authors.affiliation: Eye Center, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Daizhan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 1] Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China [2] Key Laboratory of Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Eye Center, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D003635:De Lange Syndrome / Q000235:genetics* / Q000473:pathology; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009679:Nuclear Family; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases
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