Reader TTS

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

renal failure. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full

article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs *

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

20 September 2021 SKELETAL PROGENITOR LRP1 DEFICIENCY CAUSES SEVERE AND PERSISTENT SKELETAL DEFECTS WITH WNT PATHWAY DYSREGULATION Article Open access 26 January 2025 A NEOMORPHIC VARIANT IN

SP7 ALTERS SEQUENCE SPECIFICITY AND CAUSES A HIGH-TURNOVER BONE DISORDER Article Open access 04 February 2022 REFERENCES * Johnson, R.L. & Tabin, C.J. Molecular models for vertebrate

limb development. _Cell_ 90, 979–990 (1997). Article  CAS  Google Scholar  * Chen, H _et al_. Limb and kidney defects in _Lmxlb_ mutant mice suggest an involvement of _LMX1B_ in human nail

patella syndrome. _Nature Genet._ 19, 51–55 (1998). Article  Google Scholar  * Schmeichel, K.L. & Beckerle, M.C. Molecular dissection of a LIM domain. _Mol. Biol. Cell_ 8, 219–230

(1997). Article  CAS  Google Scholar  * Feuerstein, R., Wang, X., Song, D., Cooke, N.E. & Liebhaber, S.A., LIM/double zinc-finger motif functions as a protein dimerization domain. _Proc.

Natl. Acad. Sci. USA_ 91, 10655–10659 (1994). Article  CAS  Google Scholar  * Schmeichel, K.L. & Beckerle, M.C. The LIM domain is a modular protein-binding interface. _Cell_ 79, 211–219

(1994). Article  CAS  Google Scholar  * Bang, A.G. & Goulding, M.D. Regulation of vertebrate neural cell fate by transcription factors. _Curr. Opin. Neurobiol._ 6, 25–32 (1996). Article

  CAS  Google Scholar  * Sheng, H.Z. _et al_. Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. _Science_ 272, 1004–1007 (1996). Article  CAS  Google Scholar  *

St-Jacques, B. & McMahon, A.P. Early mouse development: lessons from gene targeting. _Curr. Opin. Genet. Devel._ 6, 439–444 (1996). Article  CAS  Google Scholar  * Gill, G.N. The enigma

of LIM domains. _Structure_ 3, 1285–1289 (1995). Article  CAS  Google Scholar  * Taira, M., Evrard, J.L., Steinmetz, A. & Dawid, I.B. Classification of LIM proteins. _Trends Genet._ 11,

431–432 (1995). Article  CAS  Google Scholar  * Jones, K.L. _Smith's Recognizable Patterns of Human Malformation_ (W.B. Sauders Company, Philadelphia, 1997). * Del Pozo, E. & Lapp,

H. Ultrastructure of the kidney in the nephropathy of the nail—patella syndrome. _Am. J. Clin. Pathol._ 54, 845–851 (1970). Article  CAS  Google Scholar  * Hoyer, J.R., Michael, A.F. &

Vernier, R.L. Renal disease in nail-patella syndrome: clinical and morphologic studies. _Kidney Internatl._ 2, 231–238 (1972). Article  CAS  Google Scholar  * Morita, T. _et al_.

Nail-Patella syndrome. Light and electron microscopic studies of the kidney. _Arch. Internal Medicine_ 131, 271–277 (1973). Article  CAS  Google Scholar  * Renwick, J.H. & Lawler, S.D.

Genetic linkage between the ABO and nail-patella loci. _Ann. Hum. Genet._ 19, 312–331 (1955). Article  CAS  Google Scholar  * Mcintosh, L. _et al_. Fine Mapping of the Nail-Patella Syndrome

Locus At 9q34. _Am. J. Hum. Genet._ 60, 133–142 (1997). CAS  PubMed  PubMed Central  Google Scholar  * Campeau, E. _et al_. Linkage analysis of the nail-patella syndrome. _Am. J. Hum.

Genet._ 56, 243–247 (1995). CAS  PubMed  PubMed Central  Google Scholar  * German, M.S., Wang, J., Chadwick, R.B. & Rutter, W.J. Synergistic activation of the insulin gene by a LIM-homeo

domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. _Genes Dev._ 6, 2165–2176 (1992). Article  CAS  Google Scholar  * Johnson, J.D.,

Zhang, W.G., Rudnick, A., Rutter, W.J. & German, M.S. Transcriptional Synergy Between Lim-Homeodomain Proteins and Basic Helix-Loop-Helix Proteins -the Lim2 Domain Determines

Specificity. _Mol. Cell. Biol._ 17, 3488–3496 (1997). Article  CAS  Google Scholar  * Ausubel, F.M. _et al_. _Current Protocols in Molecular Biology._ (John Wiley & Sons, Inc., New York,

1994). * Baldini, A. & Lindsay, E.A. Mapping human YAC clones by fluorescence in situ hybridization using Alu-PCR from single yeast colonies, in _In Situ Hybridization Protocols_ (ed.

Choo, K.H.A.) 75–85 (Human Press, Inc., Clifton, 1994). * Lefebvre, V., Huang, W., Harley, V.R., Goodfellow, P.N. & de Crombrugghe, B. SOX9 is a potent activator of the

chondrocyte-specific enhancer of the pro alphal(II) collagen gene. _Mol. Cell. Biol._ 17, 2336–2346 (1997). Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND

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 

Google Scholar * Bernhard Zabel View author publications You can also search for this author inPubMed Google Scholar * William Cole View author publications You can also search for this

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

ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard

Provided by the Springer Nature SharedIt content-sharing initiative