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

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Item Type:	Article
Title:	Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome
Creators Name:	Ehmke, N., Caliebe, A., Koenig, R., Kant, S.G., Stark, Z., Cormier-Daire, V., Wieczorek, D., Gillessen-Kaesbach, G., Hoff, K., Kawalia, A., Thiele, H., Altmüller, J., Fischer-Zirnsak, B., Knaus, A., Zhu, N., Heinrich, V., Huber, C., Harabula, I., Spielmann, M., Horn, D., Kornak, U., Hecht, J., Krawitz, P.M., Nürnberg, P., Siebert, R., Manzke, H. and Mundlos, S.
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.
Keywords:	Amino Acid Sequence, Congenital Hand Deformities, DNA Sequence Analysis, Exome, Haplotypes, Heterozygote, Homozygote, Molecular Models, Molecular Sequence Data, Mutation, Oxidoreductases, Pedigree, Pierre Robin Syndrome, Sequence Alignment, Young Adult
Source:	American Journal of Human Genetics
ISSN:	0002-9297
Publisher:	Cell Press
Volume:	95
Number:	6
Page Range:	763-70
Date:	4 December 2014
Official Publication:	https://doi.org/10.1016/j.ajhg.2014.11.004
PubMed:	View item in PubMed

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