A subset of ciliopathies, including Sensenbrenner, Jeune, and short-rib polydactyly syndromes are characterized by skeletal anomalies accompanied by multiorgan defects such as chronic renal failure and retinitis pigmentosa. Through exome sequencing we identified compound heterozygous mutations in WDR19 in a Norwegian family with Sensenbrenner syndrome. In a Dutch family with the clinically overlapping Jeune syndrome, a homozygous missense mutation in the same gene was found. Both families displayed a nephronophthisis-like nephropathy. Independently, we also identified compound heterozygous WDR19 mutations by exome sequencing in a Moroccan family with isolated nephronophthisis. WDR19 encodes IFT144, a member of the intraflagellar transport (IFT) complex A that drives retrograde ciliary transport. We show that IFT144 is absent from the cilia of fibroblasts from one of the Sensenbrenner patients and that ciliary abundance and morphology is perturbed, demonstrating the ciliary pathogenesis. Our results suggest that isolated nephronophthisis, Jeune, and Sensenbrenner syndromes are clinically overlapping disorders that can result from a similar molecular cause.

The authors hypothesize that truncated decorin binds to collagen in a suboptimal way, disturbing the regularity of corneal collagen fibril formation and thereby causing corneal opacities. To the best of the authors' knowledge, this is the first description of a disorder associated with an inherited alteration in the decorin gene in humans.

Primary Sjö gren syndrome is an autoimmune disease that mainly affects exocrine glands such as the salivary and lacrimal glands. In addition, systemic involvement is common.Primary Sjö gren syndrome is of particular interest to ophthalmologists as it constitutes an important differential diagnosis in conditions with dry eye disease. In addition, ocular tests for more precisely diagnosing and monitoring primary Sjö gren syndrome have become increasingly important, and new therapeutics for local and systemic treatment evolve as a result of increased understanding of immunological mechanisms and molecular pathways in the pathogenesis of primary Sjö gren syndrome. We provide an update of interest to ophthalmologists regarding pathogenesis, diagnosis, investigative procedures, and treatment options.