Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome

Sandra D. Dreyer, Guang Zhou, Antonio Baldini, Andreas Winterpacht, Bernhard Zabel, William Cole, Randy L. Johnson, Brendan Lee

Research output: Contribution to journalArticle

387 Citations (Scopus)

Abstract

The LIM-homeodomain protein Lmx1b plays a central role in dorso-ventral patterning of the vertebrate limb1. Targeted disruption of Lmx1b results in skeletal defects including hypoplastic 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 (NPS). We show that LMX1B maps to the NPS locus and that three independent NPS 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 Lmx1b/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.

Original languageEnglish
Pages (from-to)47-50
Number of pages4
JournalNature Genetics
Volume19
Issue number1
DOIs
Publication statusPublished - 1998

Fingerprint

Nail-Patella Syndrome
LIM-Homeodomain Proteins
Kidney
Mutation
Manuscripts
Nails
Renal Insufficiency
Vertebrates
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., ... Lee, B. (1998). Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nature Genetics, 19(1), 47-50. https://doi.org/10.1038/ng0598-47

Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. / Dreyer, Sandra D.; Zhou, Guang; Baldini, Antonio; Winterpacht, Andreas; Zabel, Bernhard; Cole, William; Johnson, Randy L.; Lee, Brendan.

In: Nature Genetics, Vol. 19, No. 1, 1998, p. 47-50.

Research output: Contribution to journalArticle

Dreyer, SD, Zhou, G, Baldini, A, Winterpacht, A, Zabel, B, Cole, W, Johnson, RL & Lee, B 1998, 'Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome', Nature Genetics, vol. 19, no. 1, pp. 47-50. https://doi.org/10.1038/ng0598-47
Dreyer, Sandra D. ; Zhou, Guang ; Baldini, Antonio ; Winterpacht, Andreas ; Zabel, Bernhard ; Cole, William ; Johnson, Randy L. ; Lee, Brendan. / Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. In: Nature Genetics. 1998 ; Vol. 19, No. 1. pp. 47-50.
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