Mutations in lmx1b cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome

ABSTRACT The LIM-homeodomain protein _Lmxlb_ plays a central role in dorso-ventral patterning of the vertebrate limb1. Targeted disruption of _Lmxlb_ results in skeletal defects including

hypoplas-tic nails, absent patellae and a unique form of renal dysplasia (see accompanying manuscript by H. Chen _et al_.; ref. 2). These features are reminiscent of the dominantly inherited

skeletal malformation nail patella syndrome (NFS). We show that _LMX1B_ maps to the NFS locus and that three independent NFS patients carry de novo heterozygous mutations in this gene.

Functional studies show that one of these mutations disrupts sequence-specific DNA binding, while the other two mutations result in premature termination of translation. These data

demonstrate a unique role for _LMX1B_ in renal development and in patterning of the skeletal system, and suggest that alteration of _Lmxlb/LMX1B_ function in mice and humans results in

similar phenotypes. Furthermore, we provide evidence for the first described mutations in a LIM-homeodomain protein which account for an inherited form of abnormal skeletal patterning and

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IDENTIFICATION OF LIMB-SPECIFIC _LMX1B_ AUTO-REGULATORY MODULES WITH NAIL-PATELLA SYNDROME PATHOGENICITY Article Open access

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AFFILIATIONS * Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA Sandra D. Dreyer, Guang Zhou, Antonio Baldini & Brendan Lee * Department of

Pediatrics, University of Mainz, Germany Sandra D. Dreyer, Andreas Winterpacht & Bernhard Zabel * Department of Orthopedic Surgery, The Hospital for Sick Children, Toronto, Canada

William Cole * Department of Biochemistry and Molecular Biology, MD Anderson Cancer Center, University of Texas Medical School, Houston, USA Randy L. Johnson Authors * Sandra D. Dreyer View

author publications You can also search for this author inPubMed Google Scholar * Guang Zhou View author publications You can also search for this author inPubMed Google Scholar * Antonio

Baldini View author publications You can also search for this author inPubMed Google Scholar * Andreas Winterpacht View author publications You can also search for this author inPubMed 

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author inPubMed Google Scholar * Randy L. Johnson View author publications You can also search for this author inPubMed Google Scholar * Brendan Lee View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Brendan Lee. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE

Dreyer, S., Zhou, G., Baldini, A. _et al._ Mutations in _LMX1B_ cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. _Nat Genet_ 19, 47–50 (1998).

https://doi.org/10.1038/ng0598-47 Download citation * Received: 10 February 1998 * Accepted: 02 April 1998 * Issue Date: 01 May 1998 * DOI: https://doi.org/10.1038/ng0598-47 SHARE THIS

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