Linked Life Data

21081970

Source:http://linkedlifedata.com/resource/pubmed/id/21081970

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5438
pubmed:author
pubmed:copyrightInfo
© 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
326-33
pubmed:meshHeading
pubmed-meshheading:21081970-Adolescent, pubmed-meshheading:21081970-Adult, pubmed-meshheading:21081970-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:21081970-Child, pubmed-meshheading:21081970-Child, Preschool, pubmed-meshheading:21081970-DNA Mutational Analysis, pubmed-meshheading:21081970-Female, pubmed-meshheading:21081970-Follow-Up Studies, pubmed-meshheading:21081970-Founder Effect, pubmed-meshheading:21081970-Genetics, Population, pubmed-meshheading:21081970-Glaucoma, pubmed-meshheading:21081970-Gypsies, pubmed-meshheading:21081970-Homozygote, pubmed-meshheading:21081970-Humans, pubmed-meshheading:21081970-Infant, pubmed-meshheading:21081970-Latent TGF-beta Binding Proteins, pubmed-meshheading:21081970-Male, pubmed-meshheading:21081970-Mutation, pubmed-meshheading:21081970-Pedigree, pubmed-meshheading:21081970-Phenotype, pubmed-meshheading:21081970-Trabecular Meshwork, pubmed-meshheading:21081970-Vision, Ocular, pubmed-meshheading:21081970-Young Adult
pubmed:year
2011
pubmed:articleTitle
LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population.
pubmed:affiliation
Laboratory for Molecular Genetics, Centre for Medical Research, QEII Medical Centre, University of Western Australia, Perth, Western Australia, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't