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
. 2003 Dec;114(1):68-76.
doi: 10.1007/s00439-003-1012-7. Epub 2003 Sep 25.

Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening

Juanliang Cai  1 , Barbara K Goodman, Ankita S Patel, John B Mulliken, Lionel Van Maldergem, George E Hoganson, William A Paznekas, Ziva Ben-Neriah, Ruth Sheffer, Michael L Cunningham, Donna L Daentl, Ethylin Wang Jabs
Affiliations

Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening

Juanliang Cai et al. Hum Genet. 2003 Dec.

Abstract

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hum Mol Genet. 2000 Mar 22;9(5):813-9 - PubMed
    1. Genet Med. 2001 Mar-Apr;3(2):102-8 - PubMed
    1. Hum Mutat. 2000 Nov;16(5):431-6 - PubMed
    1. Nat Genet. 1997 Jan;15(1):42-6 - PubMed
    1. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10572-7 - PubMed

Publication types

Associated data

LinkOut - more resources