Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice

Árvai, Kristóf; Horváth, Péter; Balla, Bernadett; Tobiás, Bálint; Kató, Karina; Kirschner, Gyöngyi; Klujber, V.; Lakatos, Péter; Kósa, János P.

doi:10.1038/srep28417

Cited by 18 publications

(17 citation statements)

References 25 publications

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“…Osteogenesis imperfecta is a rare genetic connective tissue disorder with a dominant or recessive inheritance pattern and with the primary clinical manifestation involving the skeleton characterized by osteoporosis and increased susceptibility to fracture [ 6 , 8 , 11 , 12 ]. Type VIII of OI is recessive and was identified in 2006 [ 9 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Null mutation in prolyl 3-hydroxylase 1 causes type VIII of OI with severe-to-lethal bone dysplasia and over modification of the type I collagen helical region [ 8 , 11 ]. Recessive types cause OI in less than 10% of cases [ 11 , 12 ]. Recessive types VII and VIII are undistinguishable in children.…”

Section: Discussionmentioning

confidence: 99%

“…Types VII and VIII of OI vary from lethal-to-severe bone dysplasia [ 9 – 11 ]. Genes responsible for type VII and VIII of OI represent 5–7% or less than 10% of the disease [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Use of flexible intramedullary nailing in combination with an external fixator for a postoperative defect and pseudarthrosis of femur in a girl with osteogenesis imperfecta type VIII: a case report

Popkov

2018

Strategies in Trauma and Limb Reconstruction

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Telescopic rodding has been developed in order to obtain long-lasting osteosynthesis in the growing long bones of children with osteogenesis imperfecta (OI). The major and still unsolved drawback of any telescopic rod or nail design is a lack of rotational stability and, currently, no telescopic system allows immediate weight-bearing. When these problems are associated with insufficient longitudinal bone stability and diminished healing capacity, the result can be unfavourable causing secondary bone fragment displacement, delayed or non-union. This article presents a case report of operative treatment in a 9-year-old girl affected with OI type VIII complicated with postoperative defect and pseudarthrosis of the femur causing functional impairment with loss of walking ability. A combination of intramedullary flexible nailing and minimal external fixation was applied for treatment of femoral defect-pseudarthrosis in a girl of 9 years with OI type VIII. Intramedullary and extramedullary nails with wrapping of titanium nickel mesh subperiosteally provided osteosynthesis and deformity correction of the tibia of a small intramedullary canal diameter. Upright standing and walking with progressive weight-bearing was started 4 days after surgery. There were no septic or vascular complications nor complications related to Ilizarov fixator. Radiographs demonstrated bone union in the femur 46 days after surgery. At the follow-up visit 9 months after fixator removal, clinical alignment remained excellent without any relapse of deformity. Bone remodelling with restitution of medullary canal was noted on lower limb radiographs. The patient was able to stand and walk without pain with an aide or walker. At the follow-up visit 17 months after fixator removal, there was no decrease in achieved functional abilities and the treatment outcome remained satisfactory. Use of an external fixator with intramedullary nailing for treatment of postoperative pseudarthrosis in patient with severe OI (recessive form of OI, type VIII) provides longitudinal, rotational and angular stability. Furthermore, this approach ensured early functional activity and walking with full weight-bearing, both favourable conditions for bone tissue regeneration. The external fixator was applied for a short period and only for additional stability and not for progressive deformity correction or other manipulation. In addition, the combination of intramedullary and extramedullary nailing and subperiosteal titanium nickel mesh seems to be promising for osteosynthesis in the deformity correction of bones with small diameter in children with OI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Use of flexible intramedullary nailing in combination with an external fixator for a postoperative defect and pseudarthrosis of femur in a girl with osteogenesis imperfecta type VIII: a case report

Popkov

2018

Strategies in Trauma and Limb Reconstruction

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“…<10 to >150 genes) associated with a specific disorder . Such NGS disease‐targeted panels have been established for genetically heterogeneous disorders including OI and other skeletal disorders, as well as for hypophosphataemic rickets and calcium‐sensing disorders .…”

Section: Clinical Approach To the Patient With A Metabolic Bone Diseasementioning

confidence: 99%

Genetic approaches to metabolic bone diseases

Hannan

Newey

Whyte

et al. 2018

Brit J Clinical Pharma

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Metabolic bone diseases comprise a diverse group of disorders characterized by alterations in skeletal homeostasis, and are often associated with abnormal circulating concentrations of calcium, phosphate or vitamin D metabolites. These diseases commonly have a genetic basis and represent either a monogenic disorder due to a germline or somatic single gene mutation, or an oligogenic or polygenic disorder that involves variants in more than one gene. Germline single gene mutations causing Mendelian diseases typically have a high penetrance, whereas the genetic variations causing oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. Recognition of familial monogenic disorders is of clinical importance to facilitate timely investigations and management of the patient and any affected relatives. The diagnosis of monogenic metabolic bone disease requires careful clinical evaluation of the large diversity of symptoms and signs associated with these disorders. Thus, the clinician must pursue a systematic approach beginning with a detailed history and physical examination, followed by appropriate laboratory and skeletal imaging evaluations. Finally, the clinician must understand the increasing number and complexity of molecular genetic tests available to ensure their appropriate use and interpretation.

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“…Pyrosequencing, fluorescent detection of dNTP incorporation and semi-conductor sequencing technology are three approaches for gathering reliable information which can even help clinicians for making difficult therapeutical decisions. Approaching a clinical question with a help of semiconductor Ion Torrent has already been utilized for diagnosing some clinical entities and the method is able to directly perform nonoptical DNA sequencing of different genomes [3,4].…”

Section: Introductionmentioning

confidence: 99%

Next-generation Sequencing in the Clinical Decision Making in Hypertrophic Cardiomyopathy

Horváth¹,

Árvai²,

Kósa³

et al. 2017

Next Generat Sequenc & Applic

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Next generation sequencing (NGS) is becoming a valuable tool in clinical decisions. Here, we discuss the case of a family (2 parents with 3 children) with hypertrophic cardiomyopathy where we applied a NGS method developed by us to determine the genetic background of the disease. When the youngest sister underwent sudden cardiac arrest and successful reanimation, her genome was tested with this approach and two disease-causing heterozygous mutations in the MYBPC3 gene (p.R495Q and p.S593fs*11) were identified. After this, all of the family members were screened targeting these two mutations. The mother carried the frameshift mutation (p.S593fs*11) while the father's genome contained the point mutation (p.R495Q). All the children were compound heterozygous. Information collected from our genetic testing panel helped to make the decision of implanting ICD that is associated potentially severe complications in children. This case further reinforces that a full-scale, cost-effective NGS method can be utilized to supplement diagnostic and therapeutic processes of hypertrophic cardiomyopathy in clinical practice.

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Next-generation sequencing of common osteogenesis imperfecta-related genes in clinical practice

Cited by 18 publications

References 25 publications

Use of flexible intramedullary nailing in combination with an external fixator for a postoperative defect and pseudarthrosis of femur in a girl with osteogenesis imperfecta type VIII: a case report

Use of flexible intramedullary nailing in combination with an external fixator for a postoperative defect and pseudarthrosis of femur in a girl with osteogenesis imperfecta type VIII: a case report

Genetic approaches to metabolic bone diseases

Next-generation Sequencing in the Clinical Decision Making in Hypertrophic Cardiomyopathy

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