9 research outputs found
LONG-TERM SURGICAL AND VISUAL OUTCOMES IN INDIAN CHILDREN WITH DEVELOPMENTAL GLAUCOMA OPERATED ON WITHIN 6 MONTHS OF BIRTH
Syndromic Multisuture Craniosynostosis With Associated Anterior Segment Dysgenesis, Optic Nerve Hypoplasia, and Congenital Glaucoma
Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study
Combined trabeculotomy and trabeculectomy: outcome for primary congenital glaucoma in a West African population
Acute Corneal Hydrops in Children with Primary Infantile Glaucoma: A Report of 31 Cases over 23 Years at the LVPEI
LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population
Primary congenital glaucoma (PCG) is a genetically heterogeneous autosomal recessive disorder, which is an important cause of blindness in childhood. The first known gene, CYP1B1, accounts for a variable proportion of cases in most populations. A second gene, LTBP2, was recently reported in association with a syndrome, in which glaucoma is secondary to lens dislocation. We report on the molecular and clinical profile of 34 families diagnosed as PCG, all originating from the Roma/Gypsy founder population. Comprehensive sequencing analysis revealed a level of heterogeneity unusual for this population, with five CYP1B1 and one ancestral LTBP2 mutation accounting for ∼70% of patients (25 out of 37) and the remainder still unexplained. Homozygosity for the founder LTBP2 p.R299X mutation resulted in a more severe clinical phenotype and poorer outcome despite a markedly higher number of surgical interventions. The genetically homogeneous group of p.R299X homozygotes showed variable phenotypes (presumably also underlying pathogenetic mechanisms), wherein PCG proper with primary dysgenesis of the trabecular meshwork, and Marfan syndrome-like zonular disease with ectopia lentis and later onset secondary glaucoma are two extremes. The spectrum manifestations may occur in different combinations and have a different evolution even within the same sibship or a single patient. Preliminary observations on compounds with mutations in both CYP1B1-LTBP2 suggest that the observed combinations are of no clinical significance and digenic inheritance is unlikely. We provide a population genetics perspective to explain the allelic heterogeneity, comparing the history and geographic distribution of the two major founder mutations – p.R299X/LTBP2 and p.E387K/CYP1B1