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Journal Article

Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome

MPS-Authors

Fischer-Zirnsak,  B.
Max Planck Society;

Knaus,  A.
Max Planck Society;

Harabula,  I.
Max Planck Society;

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Spielmann,  M.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kornak,  U.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Hecht,  J.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Krawitz,  P. M.
Max Planck Society;

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Mundlos,  S.
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Ehmke.pdf
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Citation

Ehmke, N., Caliebe, A., Koenig, R., Kant, S. G., Stark, Z., Cormier-Daire, V., et al. (2014). Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome. The American Journal of Human Genetics, 95(6), 763-770. doi:10.1016/j.ajhg.2014.11.004.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0025-7848-D
Abstract
Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. We describe the identification of homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs( *)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction we showed that the mutation c.298G>T is probably a founder mutation. Due to the spectrum of the amino acid changes, we suggest that loss of function in TGDS is the underlying mechanism of Catel-Manzke syndrome. TGDS (dTDP-D-glucose 4,6-dehydrogenase) is a conserved protein belonging to the SDR family and probably plays a role in nucleotide sugar metabolism.