Identification of a <i>RRAGA</i> missense mutation in a four-generation Chinese family with autosomal dominant juvenile-onset progressive posterior subcapsular cataracts.

<p>(<b>A</b>) Pedigree of Family 1. Squares represent males, circles females, black symbols affected individuals, and white symbols unaffected individuals. All affected family members have juvenile-onset progressive posterior subcapsular cataracts. The arrow denotes the proband. Asterisks denote individuals with DNA collected from blood samples. Red triangles denote individuals from whom DNA was subjected to WES in the current study. Genotypes are indicated beneath the individual symbols. The heterozygous missense mutation p.Leu60Arg shows complete co-segregation with the progressive posterior subcapsular cataract phenotype. The results of slit-lamp examination for IV-13 in both OD (<b>B</b>) and OS (<b>C</b>) demonstrate deposition of dot-like opacity underneath the posterior capsule of the lens in affected family members. The age at onset in most of these affected individuals is between adolescent and early adulthood, suggesting a juvenile disease onset. (<b>D</b>) Step-by-step filtering strategy in Family 1 for the four affected individuals subjected to WES. The filtering criteria are given on the left side of the workflow. The number of variants that remain after each filtering step is shown in the workflow. The Four candidate variants were obtained as shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006090#pgen.1006090.t002" target="_blank">Table 2</a>. Among these variants a heterozygous missense mutation c.179T>G (p.Leu60Arg) in <i>RRAGA</i> was identified after Sanger confirmation of co-segregation.