Mutation of the FOXC2 gene in familial distichiasis

Brooks, Brian P.; Dagenais, Susan L.; Nelson, Christine C.; Glynn, Michael W.; Caulder, Mark S; Downs, J. Crawford; Glover, Thomas W.

doi:10.1016/s1091-8531(03)00144-7

Cited by 31 publications

(18 citation statements)

References 18 publications

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“…Various types of mutations have been found throughout the coding sequence, with approximately 30% in the FHD and approximately 60% in the C-terminal domain, from amino acids 180 to 501. Nevertheless, FOXC2 mutations in hereditary distichiasis are quite rare, and only two have been previously reported 6,7.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Han

et al. 2016

Int. J. Biol. Sci.

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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.

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Section: Discussionmentioning

confidence: 99%

“…To date, rare cases of hereditary distichiasis have been reported worldwide, but the mechanisms underlying this disease have remained unknown 7. A FOXC2 gene mutation in hereditary distichiasis has been reported in only two US families 6,7. Furthermore, the molecular mechanism of FOXC2 in hereditary distichiasis has yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Han

et al. 2016

Int. J. Biol. Sci.

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“…Distichiasis is defined as a congenital anomaly in which accessory eyelashes occur in the posterior border of the eyelid margins in the position of the meibomian gland orifices. The extra eyelashes may protrude into the cornea, producing severe corneal abrasions in 74% of patients, 4 and may be the only symptom of a FOXC2 mutation 5,6 . Lymphedema usually appears during puberty or later, but before the age of 40 years.…”

Section: Discussionmentioning

confidence: 99%

Lymphedema–distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene

et al. 2008

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Lymphedema-distichiasis syndrome (LD, OMIM 153400) is an autosomal dominant disorder with variable expression. It is caused by mutations in the FOXC2-gene, which codes for a forkhead transcription factor involved in the development of the lymphatic and vascular system. LD is characterized by late childhood or pubertal onset lymphedema of the limbs and distichiasis (double row of eyelashes). While the latter is the most common expression of LD, venous insufficiency occurs in half of the patients. Other associations have been reported, including congenital heart disease, ptosis, cleft lip/palate and spinal extradural cysts. Here we describe a family with classical lymphedema-distichiasis syndrome caused by a duplication in the FOXC2-gene.

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“…This brings to four the number of missense mutations reported by our group, S125L and R121H being those previously identified (Bell et al 2001;Brice et al 2002). We are not aware of any other missense mutations in FOXC2 being reported as causative for LD, with those previously published being either frame shift or nonsense mutations (Fang et al 2000;Finegold et al 2001;Erickson et al 2001;Bell et al 2001;Brice et al 2002;Traboulsi et al 2002;Brooks et al 2003;Yildirim-Toruner et al 2004).…”

Section: Resultsmentioning

confidence: 63%

Lymphoedema-distichiasis and FOXC2: unreported mutations, de novo mutation estimate, families without coding mutations

Sholto-Douglas-Vernon

Bell

Brice

et al. 2005

Hum Genet

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Lymphoedema-distichiasis (LD) is a syndromic form of primary lymphoedema, where mutations in the gene for the developmental transcription factor FOXC2 have been shown to be causative. The disorder has been considered very rare, but our group has now ascertained 34 families and 11 sporadic cases in the UK. Two families with LD have no mutation in the coding region of FOXC2, although both are consistent with linkage to the FOXC2 locus. A deletion has been ruled out as a possible cause of LD in these families, leaving promoter mutations as the most likely cause. Sixteen previously unpublished mutations are reported, plus an estimate of the frequency of new mutations in this disorder.

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Mutation of the FOXC2 gene in familial distichiasis

Cited by 31 publications

References 18 publications

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

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

Lymphedema–distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene

Lymphoedema-distichiasis and FOXC2: unreported mutations, de novo mutation estimate, families without coding mutations

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