Whole genome sequence analysis identifies a PAX2 mutation to establish a correct diagnosis for a syndromic form of hyperuricemia.

Hereditary hyperuricemia may occur as part of a syndromic disorder or as an isolated nonsyndromic disease, and over 20 causative genes have been identified. Here, we report the use of whole genome sequencing (WGS) to establish a diagnosis in a family in which individuals were affected with gout, hyperuricemia associated with reduced fractional excretion of uric acid, chronic kidney disease (CKD), and secondary hyperparathyroidism, that are consistent with familial juvenile hyperuricemic nephropathy (FJHN). However, single gene testing had not detected mutations in the uromodulin (UMOD) or renin (REN) genes, which cause approximately 30-90% of FJHN. WGS was therefore undertaken, and this identified a heterozygous c.226G>C (p.Gly76Arg) missense variant in the paired box gene 2 (PAX2) gene, which co-segregated with renal tubulopathy in the family. PAX2 mutations are associated with renal coloboma syndrome (RCS), which is characterized by abnormalities in renal structure and function, and anomalies of the optic nerve. Ophthalmological examination in two adult brothers affected with hyperuricemia, gout, and CKD revealed the presence of optic disc pits, consistent with optic nerve coloboma, thereby revising the diagnosis from FJHN to RCS. Thus, our results demonstrate the utility of WGS analysis in establishing the correct diagnosis in disorders with multiple etiologies.

Ocriplasmin treatment for vitreomacular traction in real life: can the indication spectrum be expanded?

PURPOSE: To evaluate the efficacy of intravitreal ocriplasmin for the resolution of vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) in the clinical setting and to assess whether the indication spectrum of this treatment modality can be expanded beyond that of the MIVI-TRUST trials. METHODS: The records of patients with VMT with or without FTMH, who were treated with intravitreal ocriplasmin were reviewed. Patients were divided in two groups. In the first group, VMT with or without FTMH was present without any other macular pathology. In the second group, VMT with or without FTMH occurred alongside of other macular disease including age-related macular degeneration, diabetic maculopathy and post-operative pseudophakic cystoid macular edema. RESULTS: Release of the VMT was achieved in 12/20 patients (12/20 eyes) of the first group. 16 eyes in this group met 3 or more criteria known to be associated with favorable prognosis after intravitreal ocriplasmin treatment. No cases of release of the VMT were observed in the second group, which included 15 patients (15 eyes). Significant improvement of visual acuity and reduction of the central macular thickness was observed only in the subgroup of eyes which responded to treatment. CONCLUSIONS: Concomitant macular pathology was a significant factor for treatment failure and we suggest that ocriplasmin should be regarded with caution in these cases. Careful patient selection for treatment with ocriplasmin using specific criteria in the clinical setting can provide superior results to those reported in the MIVI-TRUST trials.