PMID- 10053006
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 3
DP  - 1999 Mar
TI  - A novel skeletal dysplasia with developmental delay and acanthosis nigricans is
      caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.
PG  - 722-31
AB  - We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense
      mutation in four unrelated individuals with skeletal dysplasia that approaches
      the severity observed in thanatophoric dysplasia type I (TD1). However, three of 
      the four individuals developed extensive areas of acanthosis nigricans beginning 
      in early childhood, suffer from severe neurological impairments, and have
      survived past infancy without prolonged life-support measures. The FGFR3 mutation
      (A1949T: Lys650Met) occurs at the nucleotide adjacent to the TD type II (TD2)
      mutation (A1948G: Lys650Glu) and results in a different amino acid substitution
      at a highly conserved codon in the kinase domain activation loop. Transient
      transfection studies with FGFR3 mutant constructs show that the Lys650Met
      mutation causes a dramatic increase in constitutive receptor kinase activity,
      approximately three times greater than that observed with the Lys650Glu mutation.
      We refer to the phenotype caused by the Lys650Met mutation as "severe
      achondroplasia with developmental delay and acanthosis nigricans" (SADDAN)
      because it differs significantly from the phenotypes of other known FGFR3
      mutations.
FAU - Tavormina, P L
AU  - Tavormina PL
AD  - Department of Biological Chemistry, University of California, Irvine, CA, USA.
FAU - Bellus, G A
AU  - Bellus GA
FAU - Webster, M K
AU  - Webster MK
FAU - Bamshad, M J
AU  - Bamshad MJ
FAU - Fraley, A E
AU  - Fraley AE
FAU - McIntosh, I
AU  - McIntosh I
FAU - Szabo, J
AU  - Szabo J
FAU - Jiang, W
AU  - Jiang W
FAU - Jabs, E W
AU  - Jabs EW
FAU - Wilcox, W R
AU  - Wilcox WR
FAU - Wasmuth, J J
AU  - Wasmuth JJ
FAU - Donoghue, D J
AU  - Donoghue DJ
FAU - Thompson, L M
AU  - Thompson LM
FAU - Francomano, C A
AU  - Francomano CA
LA  - eng
GR  - CA40573/CA/NCI NIH HHS/United States
GR  - DE11441/DE/NIDCR NIH HHS/United States
GR  - DE12581/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.10.1 (FGFR3 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3)
SB  - IM
MH  - Acanthosis Nigricans/complications/*genetics
MH  - Achondroplasia/complications/genetics
MH  - Bone and Bones/*abnormalities/diagnostic imaging
MH  - Craniosynostoses/genetics
MH  - Developmental Disabilities/complications/*genetics
MH  - Humans
MH  - Immunoblotting
MH  - Models, Biological
MH  - Mutagenesis, Site-Directed
MH  - Mutation, Missense
MH  - Phenotype
MH  - Phosphotransferases/analysis
MH  - Point Mutation
MH  - Precipitin Tests
MH  - *Protein-Tyrosine Kinases
MH  - Radiography
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/*genetics/physiology
MH  - Thanatophoric Dysplasia/complications/diagnostic imaging/genetics
PMC - PMC1377789
EDAT- 1999/03/03 03:04
MHDA- 2000/03/21 09:00
CRDT- 1999/03/03 03:04
PHST- 1999/03/03 03:04 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/03/03 03:04 [entrez]
AID - S0002-9297(07)61709-1 [pii]
AID - 10.1086/302275 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Mar;64(3):722-31. doi: 10.1086/302275.