PMID- 10360402
OWN - NLM
STAT- MEDLINE
DCOM- 19990823
LR  - 20161124
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 84
IP  - 5
DP  - 1999 Jun 11
TI  - Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3
      mutations.
PG  - 476-80
AB  - The platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group
      of short-limb dwarfing conditions. The most common form of PLSD is thanatophoric 
      dysplasia (TD), which has been divided into two types (TD1 and TD2). Three other 
      types of PLSD, or TD variants (San Diego, Torrance, and Luton), have been
      distinguished from TD. The most notable difference between TD and the variants is
      the presence of large rough endoplasmic reticulum (rER) inclusion bodies within
      chondrocytes of the variants. We examined 22 cases of TD variants for the
      presence of missense mutations in the fibroblast growth factor receptor 3 (FGFR3)
      gene. All 17 cases of the San Diego type (PLSD-SD) were heterozygous for the same
      FGFR3 mutations found in TD1. No mutations were identified in the Torrance and
      Luton types. Large inclusion bodies were found in all 14 cases of PLSD-SD.
      Similar inclusion bodies were present in two of 72 TD1 cases, but not in 39
      controls. The material retained within the rER stained only with antibody to the 
      FGFR3 protein. The radiographic and morphologic differences between TD and
      PLSD-SD may be a consequence of other genetic factors, perhaps in the processing 
      of mutant FGFR3 molecules within the rER. The presence of rER inclusion bodies
      cannot reliably discriminate between closely related skeletal dysplasias.
FAU - Brodie, S G
AU  - Brodie SG
AD  - Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research Center,
      Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California 90048,
      USA.
FAU - Kitoh, H
AU  - Kitoh H
FAU - Lachman, R S
AU  - Lachman RS
FAU - Nolasco, L M
AU  - Nolasco LM
FAU - Mekikian, P B
AU  - Mekikian PB
FAU - Wilcox, W R
AU  - Wilcox WR
LA  - eng
GR  - 5P01-HD22657/HD/NICHD NIH HHS/United States
GR  - M01-RR00425/RR/NCRR NIH HHS/United States
GR  - P30-HD34610/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  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (Receptors, Fibroblast Growth Factor)
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  - Chondrocytes/ultrastructure
MH  - Endoplasmic Reticulum, Rough/ultrastructure
MH  - Female
MH  - Fetus/abnormalities/diagnostic imaging
MH  - Humans
MH  - Immunohistochemistry
MH  - Inclusion Bodies/ultrastructure
MH  - *Mutation, Missense
MH  - Osteochondrodysplasias/classification/diagnostic imaging/embryology/*genetics
MH  - Pregnancy
MH  - Pregnancy Trimester, Second
MH  - *Protein-Tyrosine Kinases
MH  - Radiography
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/analysis/*genetics
MH  - Thanatophoric Dysplasia/diagnostic imaging/embryology/*genetics
EDAT- 1999/06/09 10:00
MHDA- 2000/06/20 09:00
CRDT- 1999/06/09 10:00
PHST- 1999/06/09 10:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/06/09 10:00 [entrez]
AID - 10.1002/(SICI)1096-8628(19990611)84:5<476::AID-AJMG12>3.0.CO;2-X [pii]
PST - ppublish
SO  - Am J Med Genet. 1999 Jun 11;84(5):476-80.