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

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. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Citation

Nadja Ehmke, Almuth Caliebe, Rainer Koenig, Sarina G Kant, Zornitza Stark, Valérie Cormier-Daire, Dagmar Wieczorek, Gabriele Gillessen-Kaesbach, Kirstin Hoff, Amit Kawalia, Holger Thiele, Janine Altmüller, Björn Fischer-Zirnsak, Alexej Knaus, Na Zhu, Verena Heinrich, Celine Huber, Izabela Harabula, Malte Spielmann, Denise Horn, Uwe Kornak, Jochen Hecht, Peter M Krawitz, Peter Nürnberg, Reiner Siebert, Hermann Manzke, Stefan Mundlos. Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome. American journal of human genetics. 2014 Dec 04;95(6):763-70

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PMID: 25480037

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