RGD Reference Report - Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome. - Rat Genome Database

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Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome.

Authors: Dündar, Munis  Müller, Thomas  Zhang, Qi  Pan, Jing  Steinmann, Beat  Vodopiutz, Julia  Gruber, Robert  Sonoda, Tohru  Krabichler, Birgit  Utermann, Gerd  Baenziger, Jacques U  Zhang, Lijuan  Janecke, Andreas R 
Citation: Dündar M, etal., Am J Hum Genet. 2009 Dec;85(6):873-82. doi: 10.1016/j.ajhg.2009.11.010.
RGD ID: 155663488
Pubmed: PMID:20004762   (View Abstract at PubMed)
PMCID: PMC2790573   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajhg.2009.11.010   (Journal Full-text)

Adducted thumb-clubfoot syndrome is an autosomal-recessive disorder characterized by typical facial appearance, wasted build, thin and translucent skin, congenital contractures of thumbs and feet, joint instability, facial clefting, and coagulopathy, as well as heart, kidney, or intestinal defects. We elucidated the molecular basis of the disease by using a SNP array-based genome-wide linkage approach that identified distinct homozygous nonsense and missense mutations in CHST14 in each of four consanguineous families with this disease. The CHST14 gene encodes N-acetylgalactosamine 4-O-sulfotransferase 1 (D4ST1), which catalyzes 4-O sulfation of N-acetylgalactosamine in the repeating iduronic acid-alpha1,3-N-acetylgalactosamine disaccharide sequence to form dermatan sulfate. Mass spectrometry of glycosaminoglycans from a patient's fibroblasts revealed absence of dermatan sulfate and excess of chondroitin sulfate, showing that 4-O sulfation by CHST14 is essential for dermatan sulfate formation in vivo. Our results indicate that adducted thumb-clubfoot syndrome is a disorder resulting from a defect specific to dermatan sulfate biosynthesis and emphasize roles for dermatan sulfate in human development and extracellular-matrix maintenance.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ehlers-Danlos syndrome musculocontractural type 1  IAGP 155663488DNA:missense mutations and deletion:CDS:multiple (human)RGD 
Ehlers-Danlos syndrome musculocontractural type 1  ISOCHST14 (Homo sapiens)155663488; 155663488DNA:missense mutations and deletion:CDS:multiple (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Brachycephaly  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Broad forehead  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Dermal translucency  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Downslanted palpebral fissures  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Dry skin  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Flat forehead  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Hypertelorism  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Malar flattening  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Protruding ear  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Retrognathia  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Slender build  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Talipes equinovarus  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Thumb contracture  IAGP 155663488DNA:missense mutations and deletion:CDS:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Chst14  (carbohydrate sulfotransferase 14)

Genes (Mus musculus)
Chst14  (carbohydrate sulfotransferase 14)

Genes (Homo sapiens)
CHST14  (carbohydrate sulfotransferase 14)


Additional Information