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

Item Type:	Article
Title:	Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome
Creators Name:	Ehmke, N. and Caliebe, A. and Koenig, R. and Kant, S.G. and Stark, Z. and Cormier-Daire, V. and Wieczorek, D. and Gillessen-Kaesbach, G. and Hoff, K. and Kawalia, A. and Thiele, H. and Altmüller, J. and Fischer-Zirnsak, B. and Knaus, A. and Zhu, N. and Heinrich, V. and Huber, C. and Harabula, I. and Spielmann, M. and Horn, D. and Kornak, U. and Hecht, J. and Krawitz, P.M. and Nürnberg, P. and Siebert, R. and 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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