English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders

Oheim, R., Tsourdi, E., Seefried, L., Beller, G., Schubach, M., Vettorazzi, E., et al. (2022). Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders. Unpublished Manuscript.

Item is

Files

show Files
hide Files
:
JCEM_Oheim et al_2022.pdf (Any fulltext), 2MB
Name:
JCEM_Oheim et al_2022.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© The Author(s) 2022

Locators

show

Creators

show
hide
 Creators:
Oheim, Ralf , Author
Tsourdi , Elena , Author
Seefried , Lothar , Author
Beller , Gisela , Author
Schubach , Max, Author
Vettorazzi , Eik, Author
Stürznickel, Julian , Author
Rolvien , Tim, Author
Ehmke , Nadja , Author
Delsmann , Alena , Author
Genest, Franca, Author
Krüger, Ulrike , Author
Zemojtel , Tomasz , Author
Barvencik , Florian, Author
Schinke , Thorsten , Author
Jakob, Franz, Author
Hofbauer, Lorenz C. , Author
Mundlos, Stefan1, Author              
Kornak, Uwe, Author
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              

Content

show
hide
Free keywords: osteoporosis, low bone mass disorder, monogenic disorder, genetic risk score, rare genetic variant, genotype-phenotype correlation
 Abstract: Context Many different inherited and acquired conditions can result in premature bone fragility / low bone mass disorders (LBMD). Objective We aimed at elucidating the impact of genetic testing on differential diagnosis of adult LBMD and at defining clinical criteria for predicting monogenic forms. Methods Four clinical centers broadly recruited a cohort of 394 unrelated adult women before menopause and men younger than 55 years with a bone mineral density (BMD) Z-score <-2.0, and/or pathological fractures. After exclusion of secondary causes or unequivocal clinical/biochemical hallmarks of monogenic LBMD all participants were genotyped by targeted next-generation sequencing Results In total 20.8% of the participants carried rare disease-causing variants (DCV) in genes known to cause osteogenesis imperfecta (COL1A1, COL1A2), hypophosphatasia (ALPL), and early-onset osteoporosis (LRP5, PLS3, and WNT1). In addition, we identified rare DCV in ENPP1, LMNA, NOTCH2, and ZNF469. Three individuals had autosomal recessive, 75 autosomal dominant, and four X-linked disorders. 9.7% of the participants harbored variants of unknown significance. A regression analysis revealed that the likelihood of detecting a DCV correlated with a positive family history of osteoporosis, peripheral fractures (>2), and a high normal BMI. In contrast, mutation frequencies did not correlate with age, prevalent vertebral fractures, BMD, or biochemical parameters. In individuals without monogenic disease-causing rare variants, common variants predisposing for low BMD, e.g. in LRP5, were overrepresented. Conclusion The overlapping spectra of monogenic adult LBMD can be easily disentangled by genetic testing and the proposed clinical criteria can help to maximize the diagnostic yield.

Details

show
hide
Language(s): eng - English
 Dates: 2022-03-11
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1210/clinem/dgac147
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Clinical Endocrinology and Metabolism
  Other : J. Clin. Endocrinol. Metab.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Baltimore, Md. : Issued for the Endocrine Society by the Williams & Wilkins Co.
Pages: - Volume / Issue: - Sequence Number: dgac147 Start / End Page: - Identifier: ISSN: 0021-972X
CoNE: https://pure.mpg.de/cone/journals/resource/110992357321228