| Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking. | |
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MedLine Citation:
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PMID: 16980979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cranio-lenticulo-sutural dysplasia (CLSD) is an autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects mapped to chromosome 14q13-q21 (ref. 1). Here we show, using a positional cloning approach, that an F382L amino acid substitution in SEC23A segregates with this syndrome. SEC23A is an essential component of the COPII-coated vesicles that transport secretory proteins from the endoplasmic reticulum to the Golgi complex. Electron microscopy and immunofluorescence show that there is gross dilatation of the endoplasmic reticulum in fibroblasts from individuals affected with CLSD. These cells also exhibit cytoplasmic mislocalization of SEC31. Cell-free vesicle budding assays show that the F382L substitution results in loss of SEC23A function. A phenotype reminiscent of CLSD is observed in zebrafish embryos injected with sec23a-blocking morpholinos. Our observations suggest that disrupted endoplasmic reticulum export of the secretory proteins required for normal morphogenesis accounts for CLSD. |
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Authors:
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Simeon A Boyadjiev; J Christopher Fromme; Jin Ben; Samuel S Chong; Christopher Nauta; David J Hur; George Zhang; Susan Hamamoto; Randy Schekman; Mariella Ravazzola; Lelio Orci; Wafaa Eyaid |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-09-17 |
Journal Detail:
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Title: Nature genetics Volume: 38 ISSN: 1061-4036 ISO Abbreviation: Nat. Genet. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-28 Completed Date: 2006-11-28 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 1192-7 Citation Subset: IM |
Affiliation:
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McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. simeon.boyd@ucdmc.ucdavis.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics* Amino Acid Sequence Animals Cataract / genetics Disease Models, Animal Embryo, Nonmammalian Endoplasmic Reticulum / metabolism* Facial Bones / abnormalities Female Golgi Apparatus / metabolism* Humans Male Molecular Sequence Data Mutation* Pedigree Protein Transport / genetics Vesicular Transport Proteins / genetics*, metabolism* Zebrafish / embryology, genetics Zebrafish Proteins / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DE00462/DE/NIDCR NIH HHS; DE16342/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/SEC23A protein, human; 0/Vesicular Transport Proteins; 0/Zebrafish Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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