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

Am J Hum Genet. 2014 Dec 4;95(6):763-70. doi: 10.1016/j.ajhg.2014.11.004.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Child, Preschool
  • Exome / genetics
  • Female
  • Hand Deformities, Congenital / enzymology
  • Hand Deformities, Congenital / genetics*
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Pedigree
  • Pierre Robin Syndrome / enzymology
  • Pierre Robin Syndrome / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Young Adult


  • Oxidoreductases

Supplementary concepts

  • Catel Manzke syndrome