| Genomic rearrangements of the GREM1-FMN1 locus cause oligosyndactyly, radio-ulnar synostosis, hearing loss, renal defects syndrome and Cenani--Lenz-like non-syndromic oligosyndactyly. | |
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MedLine Citation:
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PMID: 20610440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Limb development is a complex process requiring proper spatio-temporal expression of a network of limb specific morphogens. Grem1 and Fmn1 play an important role in mouse and chick limb development. The mouse limb deformity (ld) phenotype with digit reduction, syndactyly, radio-ulnar synostosis, variable renal defects and absent fibulae is caused by loss of Grem1 function. This could be due to either coding Grem1 homozygous mutations or homozygous deletions of the neighbouring Fmn1 gene, which also removes limb specific regulatory sequences of Grem1. Recent studies reinforce the hypothesis that a loss of Fmn1 protein could also contribute to the observed ld anomalies. In addition, an over-expression of Grem1 in developing chick limbs represses the programmed cell death in the interdigital mesenchyme, resulting in interdigital webbing and truncation of distal cartilage elements. AIMS/RESULTS: For the first time, chromosomal imbalances in the GREM1 FMN1 region in individuals with limb defects are reported here. A 263 Kb homozygous deletion of FMN1 was associated with oligosyndactyly, radioulnar synostosis, hearing loss and renal defects, features identical to ld mice. A 1.7 Mb duplication encompassing both the GREM1 and FMN1 genes was detected in a patient with isolated Cenani-Lenz-like oligosyndactyly of the hands, resembling the transgenic chick wings in which Grem1 was over-expressed. CONCLUSIONS: The phenotypes of these two patients represent new entities/syndromes within the Cenani-Lenz clinical spectrum: (1) an autosomal recessive oligosyndactyly, radio-ulnar synostosis, hearing loss and renal defect syndrome; and (2) an autosomal dominant Cenani-Lenz-like non-syndromic oligosyndactyly. |
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Authors:
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Boyan Ivanov Dimitrov; Thierry Voet; Luc De Smet; Joris Robert Vermeesch; Koen Devriendt; Jean-Pierre Fryns; Philippe Debeer |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-07 |
Journal Detail:
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Title: Journal of medical genetics Volume: 47 ISSN: 1468-6244 ISO Abbreviation: J. Med. Genet. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-11-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985087R Medline TA: J Med Genet Country: England |
Other Details:
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Languages: eng Pagination: 569-74 Citation Subset: IM |
Affiliation:
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Centre of Human Genetics, University Hospitals Leuven, Catholic University Leuven, Leuven 3000, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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genetics*,
pathology Adult Animals Chickens Chromosome Aberrations* Chromosomes, Human, Pair 15 / genetics Female Fetal Proteins / genetics* Gene Rearrangement* Genetic Loci / genetics Genome, Human / genetics* Hearing Loss / complications, genetics Humans Infant Intercellular Signaling Peptides and Proteins / genetics* Kidney Diseases / complications*, genetics, radiography Male Mice Microfilament Proteins / genetics* Nuclear Proteins / genetics* Pedigree Phenotype Radius / abnormalities Syndactyly / complications, genetics Syndrome Ulna / abnormalities |
| Chemical | |
Reg. No./Substance:
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0/Fetal Proteins; 0/GREM1 protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/Microfilament Proteins; 0/Nuclear Proteins; 147336-47-8/formin 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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