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A nonsense mutation in MSX1 causes Witkop syndrome
D Jumlongras1, M Bei, J M Stimson
1Department of Cell Biology, Brigham and Women's Hospital, Boston, MA, USA.
American Journal of Human Genetics
|May 23, 2001
Summary
Witkop syndrome (TNS) is a rare genetic disorder causing nail and tooth abnormalities. A mutation in the MSX1 gene is identified as the cause, highlighting MSX1
Area of Science:
- Genetics
- Developmental Biology
- Oral Biology
Background:
- Witkop syndrome (TNS) is a rare autosomal dominant disorder.
- TNS is characterized by nail dysplasia and congenital tooth agenesis.
- The genetic basis of TNS remained largely unknown.
Purpose of the Study:
- To identify the gene responsible for Witkop syndrome (TNS).
- To investigate the role of MSX1 in tooth and nail development.
Main Methods:
- Candidate-gene linkage analysis in a three-generation family.
- Direct sequencing and restriction-enzyme analysis of the MSX1 gene.
- Histological analysis of Msx1-knockout mice.
Main Results:
- Linkage between TNS and markers surrounding the MSX1 locus was established.
- A heterozygous stop mutation in the MSX1 homeodomain cosegregated with TNS.
- Msx1-null mice exhibited defective nail plates and disrupted tooth development.
Conclusions:
- A nonsense mutation in MSX1 causes Witkop syndrome (TNS).
- MSX1 is essential for normal tooth and nail development.
- Msx1 plays a critical role in the development of ectodermal appendages.
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