Dataset Information

Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.

ABSTRACT:

Context

Many different inherited and acquired conditions can result in premature bone fragility/low bone mass disorders (LBMDs).

Objective

We aimed to elucidate the impact of genetic testing on differential diagnosis of adult LBMDs 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 LBMDs, all participants were genotyped by targeted next-generation sequencing.

Results

In total, 20.8% of the participants carried rare disease-causing variants (DCVs) in genes known to cause osteogenesis imperfecta (COL1A1, COL1A2), hypophosphatasia (ALPL), and early-onset osteoporosis (LRP5, PLS3, and WNT1). In addition, we identified rare DCVs in ENPP1, LMNA, NOTCH2, and ZNF469. Three individuals had autosomal recessive, 75 autosomal dominant, and 4 X-linked disorders. A total of 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 body mass index (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 (eg, 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.

SUBMITTER: Oheim R

PROVIDER: S-EPMC9202726 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.

Oheim Ralf R Tsourdi Elena E Seefried Lothar L Beller Gisela G Schubach Max M Vettorazzi Eik E Stürznickel Julian J Rolvien Tim T Ehmke Nadja N Delsmann Alena A Genest Franca F Krüger Ulrike U Zemojtel Tomasz T Barvencik Florian F Schinke Thorsten T Jakob Franz F Hofbauer Lorenz C LC Mundlos Stefan S Kornak Uwe U

The Journal of clinical endocrinology and metabolism 20220601 7

<h4>Context</h4>Many different inherited and acquired conditions can result in premature bone fragility/low bone mass disorders (LBMDs).<h4>Objective</h4>We aimed to elucidate the impact of genetic testing on differential diagnosis of adult LBMDs and at defining clinical criteria for predicting monogenic forms.<h4>Methods</h4>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. ...[more]

PMID: 35276006

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Dataset Information

Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.

Context

Objective

Methods

Results

Conclusion

Publications

Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.

Similar Datasets

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