title: Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation.
abstract: Distichiasis presents as double rows of eyelashes arising from aberrant differentiation of the meibomian glands of the eyelids, and it may be sporadic or hereditary. FOXC2 gene mutations in hereditary distichiasis are rarely reported. Here, we examined two generations of a Chinese family with hereditary distichiasis but without lymphedema or other features of LD syndrome. The FOXC2 gene was amplified and sequenced in all family members. Subcellular localization and luciferase assays were performed to assess the activity of the mutant FOXC2 protein. Clinical examinations showed distichiasis, lower eyelid ectropion, congenital ptosis and photophobia in all affected individuals. Sequence analysis revealed a novel frameshift mutation, c.964_965insG, in the coding region of the FOXC2 gene. This mutation caused protein truncation due to the presence of a premature stop codon. A fluorescence assay showed that this mutation did not change the nuclear localization of the protein. However, it impaired DNA-binding activity and decreased transcriptional activation. This is the first report of a FOXC2 mutation in hereditary distichiasis in the Chinese population. The findings of our study expand the FOXC2 mutation spectrum and contribute to the understanding of the genotype-phenotype correlation of this disease.
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Leilei
authors: L
authors: Zhang
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Jie
authors: J
authors: He
authors: Department of endocrinology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Bing
authors: B
authors: Han
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Linna
authors: L
authors: Lu
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Jiayan
authors: J
authors: Fan
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: He
authors: H
authors: Zhang
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Shengfang
authors: S
authors: Ge
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Yixiong
authors: Y
authors: Zhou
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Renbing
authors: R
authors: Jia
authors: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xianqun
authors: X
authors: Fan
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002648:Child; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005140:Eyelashes / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein; D004247:DNA
keywords: FOXC2; congenital distichiasis; mutation.