ESPEYB15 5 Bone, Growth Plate and Mineral Metabolism New genes and gene mutations (3 abstracts)
5.4 Mutations That Alter the Carboxy-Terminal-Propeptide Cleavage Site of the Chains of Type I Procollagen Are Associated With a Unique Osteogenesis Imperfecta Phenotype
Cundy T , Dray M , Delahunt J , Hald JD , Langdahl B , Li C , Szybowska M , Mohammed S , Duncan EL , McInerney-Leo AM , Wheeler PG , Roschger P , Klaushofer K , Rai J , Weis M , Eyre D , Schwarze U & Byers PH
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
To read the full abstract: J Bone Miner Res 2018;33(7):1260-1271
Osteogenesis imperfecta (OI) is characterized by early-onset skeletal fragility, often short stature, blue sclerae and some other features. OI is caused by mutations in the two genes encoding type I collagen, namely COL1A1 and COL1A2. Some previous reports have indicated that when the mutation involves the C-propeptide cleavage site in either one of the proteins encoded by these genes, the resulting phenotype could be very different, namely that of high bone mineral density and mild skeletal fragility (1). Apart from isolated patients, no larger series with this type of mutation have been reported. Here, the authors managed to recruit a large cohort including 29 subjects from 8 different families with 7 different pathogenic missense variants that alter the C-propeptide cleavage site. Based on the findings, it is clear that this rare class of pathogenic variants results in a distinctive OI phenotype with variable expression, mild to moderate disease severity, moderate fracture rate, high bone mass and increased bone mineral density. The findings suggest that high bone mass does not necessarily translate into a low fracture risk.
1. Lindahl K1, Barnes AM, Fratzl-Zelman N, Whyte MP, Hefferan TE, Makareeva E, Brusel M, Yaszemski MJ, Rubin CJ, Kindmark A, Roschger P, Klaushofer K, McAlister WH, Mumm S, Leikin S, Kessler E, Boskey AL, Ljunggren O, Marini JC. COL1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta. Hum Mutat. 2011;32:598-609.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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