PMID- 10080184
OWN - NLM
STAT- MEDLINE
DCOM- 19990331
LR  - 20220408
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 3
DP  - 1999 Mar
TI  - Heterozygous mutations in the gene encoding noggin affect human joint
      morphogenesis.
PG  - 302-4
AB  - The secreted polypeptide noggin (encoded by the Nog gene) binds and inactivates
      members of the transforming growth factor beta superfamily of signalling proteins
      (TGFbeta-FMs), such as BMP4 (ref. 1). By diffusing through extracellular matrices
      more efficiently than TGFbeta-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.
FAU - Gong, Y
AU  - Gong Y
AD  - Department of Genetics and Center for Human Genetics, Case Western Reserve
      University School of Medicine and University Hospitals of Cleveland, Ohio, USA.
FAU - Krakow, D
AU  - Krakow D
FAU - Marcelino, J
AU  - Marcelino J
FAU - Wilkin, D
AU  - Wilkin D
FAU - Chitayat, D
AU  - Chitayat D
FAU - Babul-Hirji, R
AU  - Babul-Hirji R
FAU - Hudgins, L
AU  - Hudgins L
FAU - Cremers, C W
AU  - Cremers CW
FAU - Cremers, F P
AU  - Cremers FP
FAU - Brunner, H G
AU  - Brunner HG
FAU - Reinker, K
AU  - Reinker K
FAU - Rimoin, D L
AU  - Rimoin DL
FAU - Cohn, D H
AU  - Cohn DH
FAU - Goodman, F R
AU  - Goodman FR
FAU - Reardon, W
AU  - Reardon W
FAU - Patton, M
AU  - Patton M
FAU - Francomano, C A
AU  - Francomano CA
FAU - Warman, M L
AU  - Warman ML
LA  - eng
SI  - GENBANK/AB013493
SI  - GENBANK/AF057364
SI  - GENBANK/AF095337
SI  - GENBANK/M98807
SI  - GENBANK/U31202
SI  - GENBANK/U79163
GR  - AR-43827/AR/NIAMS NIH HHS/United States
GR  - HD-01205/HD/NICHD NIH HHS/United States
GR  - HD-22657/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Carrier Proteins)
RN  - 0 (Genetic Markers)
RN  - 0 (Proteins)
RN  - 148294-77-3 (noggin protein)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Adolescent
MH  - Animals
MH  - Carrier Proteins
MH  - Cats
MH  - Chickens
MH  - Chromosome Mapping
MH  - Female
MH  - Finger Joint/abnormalities
MH  - Gene Expression Regulation, Developmental
MH  - Genetic Markers
MH  - Gorilla gorilla
MH  - Heterozygote
MH  - Humans
MH  - Joints/*abnormalities/physiology
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Morphogenesis
MH  - *Mutation
MH  - Proteins/*genetics
MH  - Sequence Analysis
MH  - Sequence Homology, Amino Acid
MH  - Sequence Homology, Nucleic Acid
MH  - Swine
MH  - Synostosis/*genetics
MH  - Xenopus laevis
MH  - Zebrafish
EDAT- 1999/03/18 03:02
MHDA- 2001/03/23 10:01
CRDT- 1999/03/18 03:02
PHST- 1999/03/18 03:02 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/03/18 03:02 [entrez]
AID - 10.1038/6821 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Mar;21(3):302-4. doi: 10.1038/6821.