Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17359
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Type: | Journal article |
Title: | A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey Disease) expands the spectrum of collagen-related disorders |
Author: | Gensure, R. Makitie, O. Barclay, C. Chan, C. DePalma, S. Bastepe, M. Abuzahra, H. Couper, R. Mundlos, S. Sillence, D. Kokko, L. Seidman, J. Cole, W. Juppner, H. |
Citation: | Journal of Clinical Investigation, 2005; 115(5):1250-1257 |
Publisher: | Amer Soc Clinical Investigation Inc |
Issue Date: | 2005 |
ISSN: | 0021-9738 1558-8238 |
Statement of Responsibility: | Robert C. Gensure, Outi Mäkitie, Catherine Barclay, Catherine Chan, Steven R. DePalma, Murat Bastepe, Hilal Abuzahra, Richard Couper, Stefan Mundlos, David Sillence, Leena Ala Kokko, Jonathan G. Seidman, William G. Cole, and Harald Jüppner |
Abstract: | Infantile cortical hyperostosis (Caffey disease) is characterized by spontaneous episodes of subperiosteal new bone formation along 1 or more bones commencing within the first 5 months of life. A genome-wide screen for genetic linkage in a large family with an autosomal dominant form of Caffey disease (ADC) revealed a locus on chromosome 17q21 (LOD score, 6.78). Affected individuals and obligate carriers were heterozygous for a missense mutation (3040CT) in exon 41 of the gene encoding the 1(I) chain of type I collagen (COL1A1), altering residue 836 (R836C) in the triple-helical domain of this chain. The same mutation was identified in affected members of 2 unrelated, smaller families with ADC, but not in 2 prenatal cases and not in more than 300 chromosomes from healthy individuals. Fibroblast cultures from an affected individual produced abnormal disulfide-bonded dimeric 1(I) chains. Dermal collagen fibrils of the same individual were larger, more variable in shape and size, and less densely packed than those in control samples. Individuals bearing the mutation, whether they had experienced an episode of cortical hyperostosis or not, had joint hyperlaxity, hyperextensible skin, and inguinal hernias resembling symptoms of a mild form of Ehlers-Danlos syndrome type III. These findings extend the spectrum of COL1A1-related diseases to include a hyperostotic disorder. |
Keywords: | Bone and Bones Fibula Tibia Chromosomes, Human, Pair 17 Dermis Humans Hyperostosis, Cortical, Congenital Collagen Type I Radiography Chromosome Mapping Pedigree Haplotypes Mutation Infant Female Male Collagen Type I, alpha 1 Chain |
Description: | Copyright © 2005 by the American Society for Clinical Investigation |
DOI: | 10.1172/JCI200522760 |
Published version: | http://www.jci.org/cgi/content/abstract/115/5/1250 |
Appears in Collections: | Aurora harvest 2 Paediatrics publications |
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