Diagnostic utility of next-generation sequence genetic panel testing in children presenting with a clinically significant fracture history

Harrington, Jennifer; AlSubaihin, Abdulmajeed; Dupuis, Lucie; Kannu, Peter; Mendoza-Londoño, Roberto; Howard, Andrew

doi:10.1007/s11657-021-00943-4

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…A genetic diagnosis can help to inform management decisions and enable genetic counselling. Currently next generation sequencing (NGS) that includes targeted gene panels, whole-exome sequencing and whole-genome sequencing, are available ( 19 , 48 , 49 ). As ~90% of all patients with OI possess COL1A1 or COL1A2 mutations, some propose screening for these two genes first in children with a suspected genetic aetiology for osteoporosis ( 50 ).…”

Section: Genetic Investigationsmentioning

confidence: 99%

“…As ~90% of all patients with OI possess COL1A1 or COL1A2 mutations, some propose screening for these two genes first in children with a suspected genetic aetiology for osteoporosis ( 50 ). In one study, NGS panel testing detected pathogenic variants in 35% of children with a clinically significant fracture history, especially in those who had early femoral fracture ( 48 ). It should however be recognised that genotype-phenotype correlations can be variable, even within the same family group.…”

Section: Genetic Investigationsmentioning

confidence: 99%

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Advances in Diagnosis and Management of Childhood Osteoporosis

Lim¹,

Moon²,

Davies³

2022

Jcrpe

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Childhood osteoporosis leads to increased propensity to fracture, and thus is an important cause of morbidity, pain and healthcare utilisation. Osteoporosis in children may be caused by a primary bone defect or secondary to an underlying medical condition and/or its treatment. Primary osteoporosis is rare, but there is an increasing number of children with risk factors for secondary osteoporosis. Therefore it is imperative that all paediatricians are aware of the diagnostic criteria and baseline investigations for childhood osteoporosis to enable timely referral to a specialist in paediatric bone health. This review will discuss the approach to diagnosis, investigation and management of childhood osteoporosis, with particular consideration to advances in molecular diagnosis of primary bone disorders, and current and emerging therapies for fracture reduction.

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Section: Genetic Investigationsmentioning

confidence: 99%

Section: Genetic Investigationsmentioning

confidence: 99%

Advances in Diagnosis and Management of Childhood Osteoporosis

Lim¹,

Moon²,

Davies³

2022

Jcrpe

View full text Add to dashboard Cite

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Update on the Genetics of Osteogenesis Imperfecta

Jovanovic,

Marini

2024

Calcif Tissue Int

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Osteogenesis imperfecta (OI) is a heterogeneous heritable skeletal dysplasia characterized by bone fragility and deformity, growth deficiency, and other secondary connective tissue defects. OI is now understood as a collagen-related disorder caused by defects of genes whose protein products interact with collagen for folding, post-translational modification, processing and trafficking, affecting bone mineralization and osteoblast differentiation. This review provides the latest updates on genetics of OI, including new developments in both dominant and rare OI forms, as well as the signaling pathways involved in OI pathophysiology. There is a special emphasis on discoveries of recessive mutations in TENT5A, MESD, KDELR2 and CCDC134 whose causality of OI types XIX, XX, XXI and XXI, respectively, is now established and expends the complexity of mechanisms underlying OI to overlap LRP5/6 and MAPK/ERK pathways. We also review in detail new discoveries connecting the known OI types to each other, which may underlie an eventual understanding of a final common pathway in OI cellular and bone biology.

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