Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation

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 heredi...

Full description

Bibliographic Details
Main Authors:	Zhang, Leilei, He, Jie, Han, Bing, Lu, Linna, Fan, Jiayan, Zhang, He, Ge, Shengfang, Zhou, Yixiong, Jia, Renbing, Fan, Xianqun
Format:	Online
Language:	English
Published:	Ivyspring International Publisher 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997055/

id	pubmed-4997055
recordtype	oai_dc
spelling	pubmed-49970552016-08-26 Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation Zhang, Leilei He, Jie Han, Bing Lu, Linna Fan, Jiayan Zhang, He Ge, Shengfang Zhou, Yixiong Jia, Renbing Fan, Xianqun Research Paper 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. Ivyspring International Publisher 2016-08-06 /pmc/articles/PMC4997055/ /pubmed/27570485 http://dx.doi.org/10.7150/ijbs.13774 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Leilei He, Jie Han, Bing Lu, Linna Fan, Jiayan Zhang, He Ge, Shengfang Zhou, Yixiong Jia, Renbing Fan, Xianqun
spellingShingle	Zhang, Leilei He, Jie Han, Bing Lu, Linna Fan, Jiayan Zhang, He Ge, Shengfang Zhou, Yixiong Jia, Renbing Fan, Xianqun Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
author_facet	Zhang, Leilei He, Jie Han, Bing Lu, Linna Fan, Jiayan Zhang, He Ge, Shengfang Zhou, Yixiong Jia, Renbing Fan, Xianqun
author_sort	Zhang, Leilei
title	Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
title_short	Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
title_full	Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
title_fullStr	Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
title_full_unstemmed	Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation
title_sort	novel foxc2 mutation in hereditary distichiasis impairs dna-binding activity and transcriptional activation
description	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.
publisher	Ivyspring International Publisher
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997055/
_version_	1613634264807505920

Novel FOXC2 Mutation in Hereditary Distichiasis Impairs DNA-Binding Activity and Transcriptional Activation

Similar Items