FOXE3 plays a significant role in autosomal recessive microphthalmia. Am J Med Genet A 2010 Mar;152A(3):582-90
Date
02/09/2010Pubmed ID
20140963Pubmed Central ID
PMC2998041DOI
10.1002/ajmg.a.33257Scopus ID
2-s2.0-77649219694 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop normally. In humans, autosomal dominant and recessive mutations in FOXE3 have been associated with variable phenotypes including anterior segment anomalies, cataract, and microphthalmia. We undertook sequencing of FOXE3 in 116 probands with a spectrum of ocular defects ranging from anterior segment dysgenesis and cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found in four of 26 probands affected with bilateral microphthalmia (15% of all bilateral microphthalmia and 100% of consanguineous families with this phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or corneal defects; no other associated systemic anomalies were observed in FOXE3-positive families. The previously reported c.720C > A (p.C240X) nonsense mutation was identified in two additional families in our sample and therefore appears to be recurrent, now reported in three independent microphthalmia families of varied ethnic backgrounds. Several missense variants were identified at varying frequencies in patient and control groups with some apparently being race-specific, which underscores the importance of utilizing race/ethnicity-matched control populations in evaluating the relevance of genetic screening results. In conclusion, FOXE3 mutations represent an important cause of nonsyndromic autosomal recessive bilateral microphthalmia.
Author List
Reis LM, Tyler RC, Schneider A, Bardakjian T, Stoler JM, Melancon SB, Semina EVAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Aphakia
Base Sequence
Child
Child, Preschool
Conserved Sequence
Cornea
DNA Primers
Eye Abnormalities
Female
Forkhead Transcription Factors
Genes, Recessive
Heterozygote
Homozygote
Humans
Infant
Male
Microphthalmos
Molecular Sequence Data
Mutation
Phenotype
Sequence Homology, Amino Acid
