| Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome. | |
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MedLine Citation:
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PMID: 20004762 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Munis Dündar; Thomas Müller; Qi Zhang; Jing Pan; Beat Steinmann; Julia Vodopiutz; Robert Gruber; Tohru Sonoda; Birgit Krabichler; Gerd Utermann; Jacques U Baenziger; Lijuan Zhang; Andreas R Janecke |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of human genetics Volume: 85 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-16 Completed Date: 2010-01-14 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 873-82 Citation Subset: IM |
Affiliation:
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Department of Medical Genetics, Erciyes University, Talas, 38039 Kayseri, Turkey. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Clubfoot / genetics* Craniofacial Abnormalities / genetics* Disaccharides / metabolism Epitopes Hand Deformities / genetics* Homozygote Humans Molecular Sequence Data Mutation* Mutation, Missense Sequence Homology, Amino Acid Sulfotransferases / genetics*, physiology* Syndrome Thumb* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HD058474-19A1/HD/NICHD NIH HHS; R01DK41738/DK/NIDDK NIH HHS; R01GM069968/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Disaccharides; 0/Epitopes; EC 2.8.2.-/Sulfotransferases; EC 2.8.2.-/dermatan-4-sulfotransferase-1 |
| Comments/Corrections | |
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