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Limb disorders

Gene: TGDS

Green List (high evidence)

TGDS (TDP-glucose 4,6-dehydratase)
EnsemblGeneIds (GRCh38): ENSG00000088451
EnsemblGeneIds (GRCh37): ENSG00000088451
OMIM: 616146, Gene2Phenotype
TGDS is in 6 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changing rating from red to green. More than 3 cases reported with variants in this gene and limb defects.
Created: 21 Nov 2019, 10:07 p.m. | Last Modified: 21 Nov 2019, 10:07 p.m.
Panel Version: 1.65
Associated with Catel-Manzke syndrome #616145 (AR) in OMIM.

PMID: 25480037 - Ehmke et al 2014 - Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. They identified 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 they showed that the mutation c.298G>T is probably a founder mutation. 1 patient showed short toes, short humeri, short femora, 3 had clinodactyly V and 1 had brachymetacarpia and scoliosis.

PMID: 26366375 - Pferdehirt et al 2015 - describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy. This patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. He has a homozygous p.Ala100Ser pathogenic variant. Both parents are heterozygous for this variant.

PMID: 28422407 - Schoner et al 2017 - report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers. Postmortem radiographs showed hypoplasia and V-shaped displacement of the second and third proximal phalanges of both hands as well as hypoplasia of the first metatarsals and the phalangeal bones of the halluces. Two compound heterozygous mutations in TGDS were found: c.298G>T; p.(Ala100Ser) and c.895G>A; p.(Asp299Asn), located in the predicted substrate binding site of TGDS. Analyses of the parents’ blood DNA confirmed biparental inheritance.
Created: 21 Nov 2019, 4:51 p.m. | Last Modified: 21 Nov 2019, 10:05 p.m.
Panel Version: 1.64

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Catel-Manzke syndrome 616145

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Catel-Manzke syndrome 616145
OMIM
616146
Clinvar variants
Variants in TGDS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 Nov 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tgds has been classified as Green List (High Evidence).

21 Nov 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: TGDS was added gene: TGDS was added to Limb disorders. Sources: Literature Mode of inheritance for gene: TGDS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TGDS were set to 25480037 Phenotypes for gene: TGDS were set to Catel-Manzke syndrome 616145 Review for gene: TGDS was set to GREEN