PMID- 12116251
OWN - NLM
STAT- MEDLINE
DCOM- 20020920
LR  - 20161124
IS  - 0148-7299 (Print)
IS  - 0148-7299 (Linking)
VI  - 110
IP  - 2
DP  - 2002 Jun 15
TI  - Genetic analysis of patients with the Saethre-Chotzen phenotype.
PG  - 136-43
AB  - Saethre-Chotzen syndrome is a common craniosynostosis syndrome characterized by 
      craniofacial and limb anomalies. Intragenic mutations of the TWIST gene within 
      7p21 have been identified as a cause of this disorder. There is phenotypic 
      overlap with other craniosynostosis syndromes, and intragenic mutations in FGFR2 
      (fibroblast growth factor receptor 2) and FGFR3 (fibroblast growth factor 
      receptor 3) have been demonstrated in the other conditions. Furthermore, complete 
      gene deletions of TWIST have also been found in a significant proportion of 
      patients with Saethre-Chotzen syndrome. We investigated 11 patients clinically 
      identified as having the Saethre-Chotzen phenotype and 4 patients with 
      craniosynostosis but without a clear diagnosis. Of the patients with the 
      Saethre-Chotzen phenotype, four were found to carry the FGFR3 P250R mutation, 
      three were found to be heterozygous for three different novel mutations in the 
      coding region of TWIST, and two were found to have a deletion of one copy of the 
      entire TWIST gene. Developmental delay was a distinguishing feature of the 
      patients with deletions, compared to patients with intragenic mutations of TWIST, 
      in agreement with the results of Johnson et al. [1998: Am J Hum Genet 
      63:1282-1293]. No mutations were found for the four patients with 
      craniosynostosis without a clear diagnosis. Therefore, 9 of our 11 patients (82%) 
      with the Saethre-Chotzen phenotype had detectable genetic changes in FGFR3 or 
      TWIST. We propose that initial screening for the FGFR3 P250R mutation, followed 
      by sequencing of TWIST and then fluorescence in situ hybridization (FISH) for 
      deletion detection of TWIST, is sufficient to detect mutations in > 80% of 
      patients with the Saethre-Chotzen phenotype.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Chun, Kathy
AU  - Chun K
AD  - Department of Pediatric Laboratory Medicine, Hospital for Sick Children and 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Teebi, Ahmad S
AU  - Teebi AS
FAU - Jung, Jack H
AU  - Jung JH
FAU - Kennedy, Shelley
AU  - Kennedy S
FAU - Laframboise, Rachel
AU  - Laframboise R
FAU - Meschino, Wendy S
AU  - Meschino WS
FAU - Nakabayashi, Kazuhiko
AU  - Nakabayashi K
FAU - Scherer, Stephen W
AU  - Scherer SW
FAU - Ray, Peter N
AU  - Ray PN
FAU - Teshima, Ikuko
AU  - Teshima I
LA  - eng
SI  - OMIM/101400
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Med Genet
JT  - American journal of medical genetics
JID - 7708900
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (TWIST1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Twist-Related Protein 1)
RN  - 9007-49-2 (DNA)
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
CIN - Am J Med Genet A. 2003 Aug 30;121A(2):188-9. PMID: 12910503
MH  - Acrocephalosyndactylia/*genetics/pathology
MH  - Child, Preschool
MH  - DNA/chemistry/genetics
MH  - DNA Mutational Analysis
MH  - Family Health
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Karyotyping
MH  - Male
MH  - Mutation, Missense
MH  - *Nuclear Proteins
MH  - Pedigree
MH  - Phenotype
MH  - *Protein-Tyrosine Kinases
MH  - Receptor, Fibroblast Growth Factor, Type 3
MH  - Receptors, Fibroblast Growth Factor/genetics
MH  - Transcription Factors/genetics
MH  - Twist-Related Protein 1
EDAT- 2002/07/13 10:00
MHDA- 2002/09/21 10:01
CRDT- 2002/07/13 10:00
PHST- 2002/07/13 10:00 [pubmed]
PHST- 2002/09/21 10:01 [medline]
PHST- 2002/07/13 10:00 [entrez]
AID - 10.1002/ajmg.10400 [doi]
PST - ppublish
SO  - Am J Med Genet. 2002 Jun 15;110(2):136-43. doi: 10.1002/ajmg.10400.