Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome

Timothy D. Howard, William A. Paznekas, Eric D. Green, Lydia C. Chiang, Nancy Ma, Rosa Isela Ortiz De Luna, Costanza Garcia Delgado, Mario Gonzalez-Ramos, Antonie Debra Kline, Ethylin Wang Jabs

Research output: Contribution to journalArticle

Abstract

Saethre-Chotzen syndrome is one of the most common autosomal dominant disorders of craniosynostosis in humans and is characterized by craniofacial and limb anomalies. The locus for Saethre-Chotzen syndrome maps to chromosome 7p21-p22. We have evaluated TWIST, a basic helix-loop-helix transcription factor, as a candidate gene for this condition because its expression pattern and mutant phenotypes in Drosophila and mouse are consistent with the Saethre-Chotzen phenotype. We mapped TWIST to human chromosome 7p21-p22 and mutational analysis reveals nonsense, missense, insertion and deletion mutations in patients. These mutations occur within the basic DNA binding, helix I and loop domains, or result in premature termination of the protein. Studies in Drosophila indicate that twist may affect the transcription of fibroblast growth factor receptors (FGFRs), another gene family implicated in human craniosynostosis. The emerging cascade of molecular components involved in craniofacial and limb development now includes TWIST, which may function as an upstream regulator of FGFRs.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalNature Genetics
Volume15
Issue number1
DOIs
StatePublished - Jan 1997
Externally publishedYes

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Acrocephalosyndactylia
Basic Helix-Loop-Helix Transcription Factors
Fibroblast Growth Factor Receptors
Craniosynostoses
Drosophila
Extremities
INDEL Mutation
Phenotype
Mutation
Nonsense Codon
Human Chromosomes
Missense Mutation
Genes
Chromosomes
DNA
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Howard, T. D., Paznekas, W. A., Green, E. D., Chiang, L. C., Ma, N., De Luna, R. I. O., ... Jabs, E. W. (1997). Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nature Genetics, 15(1), 36-41. https://doi.org/10.1038/ng0197-36

Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. / Howard, Timothy D.; Paznekas, William A.; Green, Eric D.; Chiang, Lydia C.; Ma, Nancy; De Luna, Rosa Isela Ortiz; Delgado, Costanza Garcia; Gonzalez-Ramos, Mario; Kline, Antonie Debra; Jabs, Ethylin Wang.

In: Nature Genetics, Vol. 15, No. 1, 01.1997, p. 36-41.

Research output: Contribution to journalArticle

Howard, TD, Paznekas, WA, Green, ED, Chiang, LC, Ma, N, De Luna, RIO, Delgado, CG, Gonzalez-Ramos, M, Kline, AD & Jabs, EW 1997, 'Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome', Nature Genetics, vol. 15, no. 1, pp. 36-41. https://doi.org/10.1038/ng0197-36
Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, De Luna RIO et al. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nature Genetics. 1997 Jan;15(1):36-41. https://doi.org/10.1038/ng0197-36
Howard, Timothy D. ; Paznekas, William A. ; Green, Eric D. ; Chiang, Lydia C. ; Ma, Nancy ; De Luna, Rosa Isela Ortiz ; Delgado, Costanza Garcia ; Gonzalez-Ramos, Mario ; Kline, Antonie Debra ; Jabs, Ethylin Wang. / Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. In: Nature Genetics. 1997 ; Vol. 15, No. 1. pp. 36-41.
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