| Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome. | |
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MedLine Citation:
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PMID: 9618165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nail-patella syndrome (NPS) is an inherited developmental disorder most commonly involving maldevelopment of the fingernails, kneecaps and elbow joints. NPS exhibits wide variation in phenotypic expression within and among families with respect to these features. Other skeletal abnormalities such as hip dislocation and club foot have also been reported in some individuals with NPS. There is an association between NPS and renal disease, and between NPS and open-angle glaucoma (OAG), but it is not known whether mutations in a single gene cause the observed skeletal, renal and ophthalmic abnormalities. Recently, LMX1B , a transcription factor of the LIM-homeodomain type with homologs that are important for limb development in vertebrates, was mapped to the same general location as NPS at 9q34. We sequenced a large segment of LMX1B from the genomic DNA of probands from four families with NPS and OAG, and identified four mutations: two stop codons, a deletion causing a frameshift and a missense mutation in a functionally important residue. The presence of these putative loss-of-function mutations in the DNA of individuals with NPS indicates that haploinsufficiency of LMX1B underlies this disorder. These findings help to explain the high degree of variability in the NPS phenotype, and suggest that the skeletal defects in NPS are a result of the diminished dorsoventral patterning activity of LMX1B protein during limb development. The results further suggest that the NPS and OAG phenotypes in the families studied result from mutations in a single gene, LMX1B. |
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Authors:
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D Vollrath; V L Jaramillo-Babb; M V Clough; I McIntosh; K M Scott; P R Lichter; J E Richards |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Human molecular genetics Volume: 7 ISSN: 0964-6906 ISO Abbreviation: Hum. Mol. Genet. Publication Date: 1998 Jul |
Date Detail:
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Created Date: 1999-01-12 Completed Date: 1999-01-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9208958 Medline TA: Hum Mol Genet Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 1091-8 Citation Subset: IM |
Affiliation:
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Department of Genetics, Stanford University, Stanford, CA 94305, USA. vollrath@genome.stanford.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF059572; AF059573; AF059574; AF059575 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Amino Acid Sequence Base Sequence DNA Mutational Analysis Female Genes, Homeobox* Glaucoma, Open-Angle / genetics, physiopathology Homeodomain Proteins / chemistry, genetics* Humans Linkage (Genetics) Male Middle Aged Molecular Sequence Data Nail-Patella Syndrome / genetics*, physiopathology Pedigree Point Mutation / physiology* Transcription Factors |
| Grant Support | |
ID/Acronym/Agency:
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EY09580/EY/NEI NIH HHS; EY11405/EY/NEI NIH HHS; EY11671/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Homeodomain Proteins; 0/LIM homeobox transcription factor 1 beta; 0/Transcription Factors |
| Comments/Corrections | |
Erratum In:
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Hum Mol Genet 1998 Aug;7(8):1333 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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