An unbalanced rearrangement of chromosomes 4:20 is associated with childhood osteoporosis and reduced caspase-3 levels

Kinning, E., McMillan, M., Shepherd, S., Helfrich, M., vant Hof, R., Adams, C., Read, H., Wall, D. M. and Ahmed, S. F. (2016) An unbalanced rearrangement of chromosomes 4:20 is associated with childhood osteoporosis and reduced caspase-3 levels. Journal of Pediatric Genetics, 5(3), pp. 167-173. (doi: 10.1055/s-0036-1584359) (PMID:27617159)

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Abstract

The purpose of this study was to investigate the association of a chromosome 4:20 imbalance with osteoporosis in three related children. Bone biochemistry, bone turnover markers, and dual-energy X-ray absorptiometry (DXA) scanning were performed in all three cases and bone biopsy and histomorphometry in one. The chromosome imbalance was delineated by array comparative genomic hybridization (aCGH) and analyzed for candidate genes. A potential candidate gene within the deleted region is caspase-3, previously linked to low bone mineral density (BMD) in heterozygous mice thus caspase-3 activity was measured in cases and controls. Routine bone biochemistry and markers of bone turnover did not reveal any abnormality. DXA showed reduced total and lumbar spine bone mineral content. aCGH showed an 8 megabase (Mb) deletion of terminal chromosome 4q incorporating a region previously linked to low BMD and a 15 Mb duplication of terminal chromosome 20p. Bone biopsy showed a high bone turnover state, trabecularisation of cortical bone and numerous small osteoclasts coupled with normal bone formation. Basal serum caspase-3 activity was lower in cases compared with controls. We conclude that the early-onset osteoporosis with low basal levels of caspase-3 and abnormal osteoclasts is a feature of this chromosomal translocation. Further investigation of the role of the deleted and duplicated genes and especially caspase-3 is required.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shepherd, Dr Sheila and McMillan, Mr Martin and Read, Ms Heather and Ahmed, Professor Syed Faisal and Wall, Dr Daniel
Authors: Kinning, E., McMillan, M., Shepherd, S., Helfrich, M., vant Hof, R., Adams, C., Read, H., Wall, D. M., and Ahmed, S. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Pediatric Genetics
Publisher:IOS Press
ISSN:2146-4596
Published Online:03 June 2016

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