In this study, we identified five novel mutations (c.154 T > C in GJA8, c.1152_1153insG in GJA3, c.1804G > C in BFSP1, c.1532C > T in EPHA2, c.356G > A in HSF4) in five Chinese families with hereditary cataracts, respectively.
Whole genome transcriptome analysis (RNA-Seq) on RNA isolated from wildtype larvae and larvae with eye defects that were putative homozygotes for the foxe3 indel variant found significant dysregulation of genes expressed in the lens and eye whose orthologues are associated with cataracts in human patients, including cryba2a, cryba1l1, mipa and hsf4.
Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure.
Our demonstration that HSF4cataract causative mutations abrogate the induction of DLAD expression reveals a novel molecular mechanism regarding how HSF4 mutations cause cataractogenesis.
Heat shock transcription factor 4 (HSF4) is related with human autosomal dominant lamellar and Marner cataracts; a T→C transition at nucleotide 348 was found in a large Chinese cataract family.
The goal of this study was to functionally evaluate the mutant HSF4(lop11) protein and to establish the onset and progression of cataracts in lop11 lenses.
Transcription activity analysis using the dual-luciferase system suggested that these cataract-relevant genes are the direct downstream targets of HSF4.
To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667).
These results identified a novel missense mutation R74H in the transcription factor gene HSF4 in a Chinese cataract family and expand the spectrum of HSF4 mutations causing cataract.
In humans, missense mutation in the hsf4 gene causes cataract, and mice bearing a targeted disruption of the hsf4 gene exhibit defects in lens fiber cell differentiation and early cataract formation.
The HSF4 mutations have been reported in four families with autosomal dominant cataracts and, recently, in a single kindred with autosomal recessive congenital cataract.
The HSF4 mutations have been reported in four families with autosomal dominant cataracts and, recently, in a single kindred with autosomal recessive congenital cataract.