title: HSF4 mutation p.Arg116His found in age-related cataracts and in normal populations produces childhood lamellar cataract in transgenic mice.
abstract: The p.Arg116His mutation in the heat shock transcription factor-4 (HSF4) has been associated with age-related cataracts, but it is also seen in 2% of the normal population, indicating either reduced penetrance or that the normal subjects were not old enough to express the phenotype. Based on the proximity of p.Arg116His to two known mutations in the DNA-binding domain of HSF4, namely, p.Leu114Pro and p.Arg119Cys, which segregate with childhood lamellar cataract, we tested the possibility that this phenotype may have been missed by the ophthalmologist and/or that it did not spread to the visual axis so as to affect vision significantly. Here, we demonstrate via BAC (bacterial artificial chromosome) transgenesis that p.Arg116His recreates the childhood lamellar cataract in mice suggesting that incomplete penetrance associated with early cataracts may not be an absence but a limitation of the detection of the phenotype.
authors: Jules Stein Eye Institute.
authors: Zhe
authors: Z
authors: Jing
authors: Rajendra K
authors: RK
authors: Gangalum
authors: Ankur M
authors: AM
authors: Bhat
authors: Yoshiko
authors: Y
authors: Nagaoka
authors: Meisheng
authors: M
authors: Jiang
authors: Suraj P
authors: SP
authors: Bhat
mesh_terms: D000367:Age Factors; D019943:Amino Acid Substitution; D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D019683:Penetrance; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors
keywords: BAC recombineering; HSF4; cataract; ocular lens; transgenic mice