G3: Genes|Genomes|Genetics · 5 authors, 5 centres
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Whole-exome sequencing of the Emory (Em/J) cataract mouse mutant excluded over 450 known cataract genes and prioritized three candidate genes with novel variants: Prx, Adamts10, and Abhd12. The study suggests Abhd12 is the most promising candidate for the mouse cataract phenotype.
Researchers used whole-exome sequencing to identify the genetic defect causing hereditary cataract in the Emory (Em/J) mouse mutant, a proposed animal model for age-related cataract. They confirmed the cataract phenotype in homozygous Em/J mice at 6–8 months of age. Sequencing analysis excluded mutations in over 450 known genes for inherited and age-related cataracts. The study identified three novel, homozygous variants in candidate genes: missense substitutions in Prx and Adamts10, and a disruptive in-frame deletion in Abhd12, all absent in control mice. In silico analysis predicted the Abhd12 variant to be strongly damaging, while the others were neutral or borderline. Human orthologs of Adamts10 and Abhd12 are associated with syndromic forms of cataract. The authors conclude that while Prx and Adamts10 cannot be excluded, Abhd12 is a promising candidate gene, and the Em/J mouse may be a model for human PHARC syndrome. The study is limited by the inability to definitively map the Em locus and the need for functional validation, such as gene editing.
