Novel Intragenic Deletion in a Pedigree with Aniridia, Morbid Obesity, and Diabetes.

: Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficiency, and glaucoma. Large chromosomal deletions spanning the gene cause WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability [formerly called mental retardation]). We describe clinical and genetic studies of a three-generation pedigree with aniridia along with additional systemic conditions (morbid obesity, diabetes) suggesting the possibility of a contiguous-gene syndrome like WAGR.: Clinical records were obtained and DNA was prepared from blood samples from three of the four patients and tested for mutations in the coding sequences of the gene. The index patient also had cardiomyopathy and was tested for known cardiomyopathy genetic mutations using a next-generation DNA sequencing assay.: We discovered a novel intragenic mutation, a 16 bp heterozygous deletion c.203delCCAGGGCAATCGGTGG, with Sanger sequencing that is the likely cause of autosomal dominant aniridia in this pedigree. This deletion causes a frameshift in predicted protein translation and a subsequent premature termination, p.Pro68Leufs*6. The deletion was detected in all three available family members with aniridia, the index patient, his mother, and his maternal aunt but was not observed in the ome ggregation onsortium (ExAC) database. Targeted sequencing of known cardiomyopathy genes in the index patient identified a second mutation, a 1.7 Mp deletion that spans the gene.: We report a pedigree with aniridia and other systemic abnormalities that were initially suspicious for a contiguous-gene syndrome like WAGR. However, genetic analysis of the pedigree revealed two independent genetic abnormalities on chromosome 11p: 1) a novel mutation, and 2) a large chromosome deletion spanning , a known cardiomyopathy gene. It is unclear if morbid obesity and type II diabetes mellitus have a related genetic cause.