Brad T. Tinkle, M.D., Ph.D. is a Clinical Geneticist. He is an Assistant Professor of Clinical Pediatrics, affiliated at the Cincinnati Children's Hospital Medical Center. The primary focus of his research is the clinical aspects and genetic basis of connective tissue disorders.
A genetic approach to fracture epidemiology in childhood†
Article first published online: 8 NOV 2005
Copyright © 2005 Wiley-Liss, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Connective Tissue Disorders
Volume 139C, Issue 1, pages 38–54, 15 November 2005
How to Cite
Tinkle, B. T. and Wenstrup, R. J. (2005), A genetic approach to fracture epidemiology in childhood. Am. J. Med. Genet., 139C: 38–54. doi: 10.1002/ajmg.c.30073
One major NIH supported laboratory effort utilizes cultured human Ehlers-Danlos syndrome (EDS) cells lacking a gene for type V collagen and a col5a1 knockout mouse to elucidate the role of the proα1(V) chain of type V collagen in collagen fibril nucleation, fibril diameter and biomechanical characteristics of connective tissues. A second major NIH supported laboratory initiative involves use of animal models and cell culture models of the heritable brittle bone disease osteogenesis imperfecta to test the efficacy of multimeric hammerhead ribozymes designed to specifically cleave the mRNA products of the mutant alleles in the more severe forms of the disease. He also designs and implements trials of new therapies for patients with osteopenia secondary to inherited diseases, including osteogenesis imperfecta and Gaucher disease.
- Issue published online: 18 NOV 2005
- Article first published online: 8 NOV 2005
- NIH. Grant Number: R01 AR47054
- osteogenesis imperfecta;
- non-accidental trauma;
- fracture recurrence;
- multiple fractures;
The purpose of this report is to provide a review of both childhood fracture epidemiology and known heritable causes for fracture predisposition to the Medical Geneticist, who is frequently consulted to assess children with multiple or unexplained fractures for a physiologic etiology. A detailed knowledge of the clinical and laboratory evaluation for osteogenesis imperfecta (OI) and other single-gene disorders is obviously essential to complete a useful evaluation of such children. The experienced clinician will immediately recognize that single gene disorders represent only a small fraction of these patients. In infants, non-accidental trauma (NAT) unfortunately is the likely explanation for the fracture pattern, but in some infants, and certainly in older children with recurrent fractures, no medical explanations can be found. Recent studies in which bone mineral density (BMD) has been associated with genetic variation at a number of candidate genes are promising but these studies are too premature yet to be used clinically. Nonetheless, we do expect that in the future whole-genome approaches in conjunction with key clinical and epidemiological variables may be combined through an informatics approach to create better predictors of fracture susceptibility for these populations of patients. © 2005 Wiley-Liss, Inc.