PMID- 14513358
OWN - NLM
STAT- MEDLINE
DCOM- 20040323
LR  - 20181113
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 114
IP  - 1
DP  - 2003 Dec
TI  - Increased risk for developmental delay in Saethre-Chotzen syndrome is associated 
      with TWIST deletions: an improved strategy for TWIST mutation screening.
PG  - 68-76
AB  - The majority of patients with Saethre-Chotzen syndrome have mutations in the 
      TWIST gene, which codes for a basic helix-loop-helix transcription factor. Of the 
      genetic alterations identified in TWIST, nonsense mutations, frameshifts 
      secondary to small deletions or insertions, and large deletions implicate 
      haploinsufficiency as the pathogenic mechanism. We identified three novel 
      intragenic mutations and six deletions in our patients by using a new strategy to 
      screen for TWIST mutations. We used polymerase chain reaction (PCR) amplification 
      with subsequent sequencing to identify point mutations and small insertions or 
      deletions in the coding region, and real-time PCR-based gene dosage analysis to 
      identify large deletions encompassing the gene, with confirmation by 
      microsatellite and fluorescence in situ hybridization (FISH) analyses. The size 
      of the deletions can also be analyzed by using the gene dosage assay with "PCR 
      walking" across the critical region. In 55 patients with features of 
      Saethre-Chotzen syndrome, 11% were detected to have deletions by real-time gene 
      dosage analysis. Two patients had a translocation or inversion at least 260 kb 3' 
      of the gene, suggesting they had position-effect mutations. Of the 37 patients 
      with classic features of Saethre-Chotzen syndrome, the overall detection rate for 
      TWIST mutations was 68%. The risk for developmental delay in patients with 
      deletions involving the TWIST gene is approximately 90% or eight times more 
      common than in patients with intragenic mutations.
FAU - Cai, Juanliang
AU  - Cai J
AD  - Department of Pediatrics, The Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - Goodman, Barbara K
AU  - Goodman BK
FAU - Patel, Ankita S
AU  - Patel AS
FAU - Mulliken, John B
AU  - Mulliken JB
FAU - Van Maldergem, Lionel
AU  - Van Maldergem L
FAU - Hoganson, George E
AU  - Hoganson GE
FAU - Paznekas, William A
AU  - Paznekas WA
FAU - Ben-Neriah, Ziva
AU  - Ben-Neriah Z
FAU - Sheffer, Ruth
AU  - Sheffer R
FAU - Cunningham, Michael L
AU  - Cunningham ML
FAU - Daentl, Donna L
AU  - Daentl DL
FAU - Jabs, Ethylin Wang
AU  - Jabs EW
LA  - eng
SI  - OMIM/101400
GR  - M01 RR0052/RR/NCRR NIH HHS/United States
GR  - P60 DE13078/DE/NIDCR NIH HHS/United States
GR  - R01 HD24061/HD/NICHD NIH HHS/United States
GR  - T32 GM07814/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030925
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (DNA Primers)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TWIST1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Twist-Related Protein 1)
SB  - IM
MH  - Acrocephalosyndactylia/*genetics
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - DNA Primers
MH  - Helix-Loop-Helix Motifs
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - *Mutation
MH  - *Nuclear Proteins
MH  - Polymerase Chain Reaction
MH  - Reference Values
MH  - *Sequence Deletion/*genetics
MH  - Transcription Factors/*genetics
MH  - Twist-Related Protein 1
EDAT- 2003/09/27 05:00
MHDA- 2004/03/24 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/06/19 00:00 [received]
PHST- 2003/07/18 00:00 [accepted]
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2004/03/24 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - 10.1007/s00439-003-1012-7 [doi]
PST - ppublish
SO  - Hum Genet. 2003 Dec;114(1):68-76. doi: 10.1007/s00439-003-1012-7. Epub 2003 Sep 
      25.