Linked Life Data

15928687

Source:http://linkedlifedata.com/resource/pubmed/id/15928687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-7-25
pubmed:abstractText
Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1018-4813
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
935-46
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15928687-Adolescent, pubmed-meshheading:15928687-Adult, pubmed-meshheading:15928687-Cohort Studies, pubmed-meshheading:15928687-DNA Mutational Analysis, pubmed-meshheading:15928687-Family, pubmed-meshheading:15928687-Female, pubmed-meshheading:15928687-Genetic Linkage, pubmed-meshheading:15928687-Genotype, pubmed-meshheading:15928687-Homeodomain Proteins, pubmed-meshheading:15928687-Humans, pubmed-meshheading:15928687-Kidney Diseases, pubmed-meshheading:15928687-LIM-Homeodomain Proteins, pubmed-meshheading:15928687-Male, pubmed-meshheading:15928687-Middle Aged, pubmed-meshheading:15928687-Mutation, pubmed-meshheading:15928687-Nail-Patella Syndrome, pubmed-meshheading:15928687-Pedigree, pubmed-meshheading:15928687-Phenotype, pubmed-meshheading:15928687-Transcription Factors
pubmed:year
2005
pubmed:articleTitle
Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.
pubmed:affiliation
Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands. t.g.j.derks@bkk.umcg.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't