Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1999 Mar;64(3):722-31.
doi: 10.1086/302275.

A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene

P L Tavormina  1 , G A Bellus, M K Webster, M J Bamshad, A E Fraley, I McIntosh, J Szabo, W Jiang, E W Jabs, W R Wilcox, J J Wasmuth, D J Donoghue, L M Thompson, C A Francomano
Affiliations

A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene

P L Tavormina et al. Am J Hum Genet. 1999 Mar.

Abstract

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Nat Genet. 1996 Oct;14(2):174-6 - PubMed
    1. J Biol Chem. 1996 Oct 4;271(40):25049-57 - PubMed
    1. Nature. 1997 Mar 20;386(6622):288-92 - PubMed
    1. Am J Med Genet. 1997 Jun 27;70(4):427-36 - PubMed
    1. Am J Dis Child. 1971 Aug;122(2):95-104 - PubMed

Publication types

MeSH terms

Substances