Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype

American Journal of Human Genetics
G A BellusC A Francomano


The fibroblast growth factor-receptor 3 (FGFR3) Lys650 codon is located within a critical region of the tyrosine kinase-domain activation loop. Two missense mutations in this codon are known to result in strong constitutive activation of the FGFR3 tyrosine kinase and cause three different skeletal dysplasia syndromes-thanatophoric dysplasia type II (TD2) (A1948G [Lys650Glu]) and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) syndrome and thanatophoric dysplasia type I (TD1) (both due to A1949T [Lys650Met]). Other mutations within the FGFR3 tyrosine kinase domain (e.g., C1620A or C1620G [both resulting in Asn540Lys]) are known to cause hypochondroplasia, a relatively common but milder skeletal dysplasia. In 90 individuals with suspected clinical diagnoses of hypochondroplasia who do not have Asn540Lys mutations, we screened for mutations, in FGFR3 exon 15, that would disrupt a unique BbsI restriction site that includes the Lys650 codon. We report here the discovery of three novel mutations (G1950T and G1950C [both resulting in Lys650Asn] and A1948C [Lys650Gln]) occurring in six individuals from five families. Several physical and radiological features of these individuals were significantly mild...Continue Reading


May 24, 2005·European Journal of Pediatrics·Felix G RiepeWolfgang G Sippell
Dec 11, 2008·Journal of Bone and Mineral Metabolism·Daisuke HaradaYoshiki Seino
Feb 7, 2008·Journal of Materials Science. Materials in Medicine·Annalisa PalmieriFrancesco Carinci
Nov 28, 2002·The British Journal of Dermatology·D TorleyC S Munro
Apr 22, 2009·Development, Growth & Differentiation·Tomoko Iwata, Robert F Hevner
Jul 15, 2006·The Journal of Clinical Investigation·Christian HafnerArndt Hartmann
Mar 26, 2013·PloS One·Nadine ReintjesBernd Wollnik
Aug 12, 2009·Future Oncology·Liang ChengAntonio Lopez-Beltran
Jan 19, 2006·Annals of Human Biology·Virginia FanoHoracio Lejarraga
Jan 29, 2016·Journal of the European Academy of Dermatology and Venereology : JEADV·S IchiyamaA Kubo
Sep 19, 2002·The Journal of Pathology·Bas W G van RhijnTheo H van der Kwast
Apr 23, 2003·American Journal of Medical Genetics. Part a·Christel Thauvin-RobinetMartine Le Merrer
Mar 4, 2011·Trends in Molecular Medicine·Heidi Greulich, Pamela M Pollock
Nov 26, 2010·Human Pathology·Liang ChengRodolfo Montironi
Dec 22, 2015·Seminars in Cell & Developmental Biology·Shahida Moosa, Bernd Wollnik
Mar 11, 2008·Best Practice & Research. Clinical Rheumatology·Geneviève BaujatMartine Le Merrer
Jul 17, 2007·Lancet·William A HortonJacqueline T Hecht
Jun 16, 2015·Connective Tissue Research·Jyoti Narayana, William A Horton
Jul 29, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Anastasia E KonstantinidouEfstratios Patsouris
Nov 21, 2012·American Journal of Medical Genetics. Part a·Tarja LinnankiviSanna Toiviainen-Salo
Jun 28, 2013·American Journal of Medical Genetics. Part a·Jennifer M KalishMatthew A Deardorff
Sep 13, 2011·American Journal of Medical Genetics. Part a·Angeliki HatzakiVoula Velissariou
Feb 4, 2012·American Journal of Medical Genetics. Part a·Tomoko SaitoMakoto Uchiyama
Jan 24, 2015·Molecular Genetics & Genomic Medicine·Yuan XueWilliam R Wilcox
Dec 25, 2009·American Journal of Medical Genetics. Part a·María Luisa Martínez-FríasECEMC Working Group
Mar 8, 2005·Experimental Cell Research·Corine G M L'Hôte, Margaret A Knowles
Jul 11, 2015·Human Molecular Genetics·Laura M McDonellSarah L Sawyer
May 25, 2015·Cytokine & Growth Factor Reviews·Leandro H GalloDaniel J Donoghue
Jun 30, 2011·The Biochemical Journal·Jørgen WescheEllen Margrethe Haugsten
Jan 1, 2006·Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology·Mitsukazu MamadaTatsutoshi Nakahata
Mar 18, 2015·European Journal of Endocrinology·Sarina G KantMonique Losekoot


Oct 1, 1979·Radiology·B D Hall, J Spranger
Mar 1, 1973·Journal of Medical Genetics·V A McKusickJ P Dorst
Jan 1, 1984·Acta Neuropathologica·K L HoJ L Chason
Jun 1, 1995·Journal of Medical Genetics·I StoilovT Costa
Sep 1, 1996·Journal of Medical Genetics·F RousseauMartine Le Merrer
Jul 22, 1998·The Journal of Pediatrics·U RamaswamiC G Brook
Dec 16, 1998·The Journal of Bone and Joint Surgery. British Volume·Y MatsuiT Ochi

Related Concepts

Thanatophoric Dysplasia, TYPE I (Disorder)
Thanatophoric Dysplasia, Type 1
Bone Diseases, Developmental
Thanatophoric Dysplasia, Type 2
Restriction Site

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Synapse Loss as Therapeutic Target in MS

As we age, the number of synapses present in the human brain starts to decline, but in neurodegenerative diseases this occurs at an accelerated rate. In MS, it has been shown that there is a reduction in synaptic density, which presents a potential target for treatment. Here is the latest research on synapse loss as a therapeutic target in MS.

Artificial Intelligence in Cardiac Imaging

Artificial intelligence (ai) techniques are increasingly applied to cardiovascular (cv) medicine in cardiac imaging analysis. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Social Learning

Social learning involves learning new behaviors through observation, imitation and modeling. Follow this feed to stay up to date on the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Single Cell Chromatin Profiling

Techniques like ATAC-seq and CUT&Tag have the potential to allow single cell profiling of chromatin accessibility, histones, and TFs. This will provide novel insight into cellular heterogeneity and cell states. Discover the latest research on single cell chromatin profiling here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.