Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis

Yaoqin Gong, Deborah Krakow, Jose Marcelino, Douglas Wilkin, David Chitayat, Riyana Babul-Hirji, Louanne Hudgins, Cor W. Cremers, Frans P.M. Cremers, Han G. Brunner, Kent Reinker, David L. Rimoin, Daniel H. Cohn, Frances R. Goodman, William Reardon, Michael Patton, Clair A. Francomano, Matthew L. Warman

Resultado de la investigación: Articlerevisión exhaustiva

274 Citas (Scopus)

Resumen

The secreted polypeptide noggin (encoded by the Nog gene) binds and inactivates members of the transforming growth factor β superfamily of signalling proteins (TGFβ-FMs), such as BMP4 (ref. 1). By diffusing through extracellular matrices more efficiently than TGFβ-FMs, noggin may have a principal role in creating morphogenic gradients. During mouse embryogenesis, Nog is expressed at multiple sites, including developing bones. Nog(-/-) mice die at birth from multiple defects that include bony fusion of the appendicular skeleton. We have identified five dominant human NOG mutations in unrelated families segregating proximal symphalangism (SYM1; OMIM 185800) and a de novo mutation in a patient with unaffected parents. We also found a dominant NOG mutation in a family segregating multiple synostoses syndrome (SYNS1; OMIM 186500); both SYM1 and SYNS1 have multiple joint fusion as their principal feature. All seven NOG mutations alter evolutionarily conserved amino acid residues. The findings reported here confirm that NOG is essential for joint formation and suggest that NOG requirements during skeletogenesis differ between species and between specific skeletal elements within species.

Idioma originalEnglish (US)
Páginas (desde-hasta)302-304
Número de páginas3
PublicaciónNature Genetics
Volumen21
N.º3
DOI
EstadoPublished - mar. 1999
Publicado de forma externa

ASJC Scopus subject areas

  • Genetics

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