Searchable abstracts of presentations at key conferences on calcified tissues

ba0004p138 | (1) | ICCBH2015

In-depth phenotyping including analyses of skin connective tissue in osteogenesis imperfecta

Balasubramanian Meena , Bishop Nick

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. Several other genes are associated with the autosomal recessive forms of OI. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissu...

ba0004p186 | (1) | ICCBH2015

Cole-Carpenter syndrome

Balasubramanian Meena , Bishop Nick

Cole-Carpenter syndrome (OMIM 112240) is characterised by bone fragility, craniosynostosis, ocular proptosis, hydrocephalus and a distinctive facial appearance. Intelligence is reported to be normal. In 1986, Cole and Carpenter reported two unrelated infants with multiple fractures and deformities of bone, with a skeletal phenotype similar to severe osteogenesis imperfecta (OI). In addition, these patients also had proptosis, blue sclerae, hydrocephalus and a distinct facial g...

ba0002p163 | (1) | ICCBH2013

Phenotype–genotype correlation and role of ancillary investigations in atypical and rare forms of osteogenesis imperfecta

Balasubramanian Meena , Parker Michael , Bishop Nicholas J

Background: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. It is a variable condition with a range of clinical severity. About 90% of patients with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes, which shows an autosomal dominant pattern (AD) of inheritance. Other genes are associated with the autosomal recessive (AR) ...

ba0007oc20 | (1) | ICCBH2019

Identifying the role of NBAS in bone fragility using zebrafish and exploring therapeutic targets to reverse NBAS activity

Balasubramanian Meena , Baxendale Sarah , Roehl Henry

Background: We discovered that variants in NBAS (Neuroblastoma Amplified Sequence Gene) known to be associated with acute liver failure are also responsible for skeletal abnormalities. This work was published as a novel cause of bone fragility [Balasubramanian et al., 2017]. NBAS role in bone fragility provides an opportunity to use tractable animal research to advance understanding of mechanism and identify potential new treatments. This would be beneficial to patien...

ba0007p10 | (1) | ICCBH2019

Radiographic evidence of zoledronic acid given during pregnancy – a case report

Peacock Amanda , Offiah AC , Balasubramanian Meena , Bishop Nick , Arundel Paul

Background: A 3.2 year old boy was reviewed following 2 low trauma femoral fractures. He had been born at 31 weeks gestation, his mother having been diagnosed with metastatic breast cancer at 12 weeks gestation. She received chemotherapy at 20 weeks gestation and was given intravenous zoledronic acid (ZA) during the second trimester for hypercalcaemia.Presenting problem: At 2.7 years, he fell on a tarmacked surface sustaining a diaphyseal fracture of his...

ba0007p216 | (1) | ICCBH2019

Dual diagnosis of autism and osteogenesis imperfecta: Case examples to illustrate the implications of dual diagnosis for enhanced outcomes for child and family

Jones Rebecca , Seasman Alison , Marr Caroline , Bishop Nicholas , Arundel Paul , Balasubramanian Meena , Team Metabolic Bone

Background: A minority of children with Osteogenesis Imperfecta (OI) seen within the Sheffield National Severe, Complex and Atypical Service (SCAOI) were also identified as showing symptoms consistent with an Autism Spectrum Disorder (ASD) (Balasubramanian et al. 2018). Diagnosis of ASD in conjunction with OI may be delayed due to presenting problems being inappropriately attributed to OI resulting in specialised ASD input not being received by children.<p class="...

ba0006p042 | (1) | ICCBH2017

Osteogenesis imperfecta type VI presenting as suspected physical abuse -- a report of two cases

Sithambaram Sivagamy , Bishop Nick , Shankar Lata , Offiah Amaka C , Pollitt Rebecca C , Balasubramanian Meena , Saggar Anand K , Arundel Paul

Background: Osteogenesis imperfecta (OI) type VI is a rare recessive disease that may present with long bone fractures in early childhood. Bone in this condition is particularly brittle; the resulting pattern of long bone fractures and lack of distinct radiographic findings can make the diagnosis less obvious than in other types of OI. We report 2 unrelated children who presented with long bone fractures and were suspected of having suffered physical abuse with removal of pare...

ba0006lb14 | (1) | ICCBH2017

P4HB recurrent missense mutation causing Cole-Carpenter syndrome: exploring the underlying mechanism

Balasubramanian Meena , Padidela Raja , Pollitt Rebecca , Bishop Nick , Mughal Zulf , Offiah Amaka , Wagner Bart , McCaughey Janine , Stephens David

Cole-Carpenter syndrome (CCS) is commonly classified as a rare Osteogenesis Imperfecta disorder. This was following the description of two unrelated patients with very similar phenotypes who were subsequently shown to have a heterozygous missense mutation in P4HB. Here, we report a 3-year old female patient who was diagnosed with a severe form of OI. Exome sequencing identified the same missense mutation in P4HB as reported in the original cohort, thus reinfo...

ba0004op1 | (1) | ICCBH2015

Skeletal and bone material phenotype in recessive osteogenesis imperfecta due to a novel homozygous point mutation in TMEM38B

Webb Emma , Balasubramanian Meena , Cole Trevor , Stewart Sue , Crabtree Nicola , Vogt Julie , Roschger Paul , Fratzl-Zelman Nadja , Klaushofer Klaus , Hogler Wolfgang

Osteogenesis imperfecta (OI) classification has recently been broadened to include genes that primarily affect osteoblast differentiation. TMEM38B encodes TRIC-B, a ubiquitously expressed monovalent cation-specific channel protein involved in calcium release from the endoplasmic reticulum. How alterations in TMEM38B cause OI remains poorly understood and bone matrix characteristics in affected patients have not previously been described.<p class="abstext"...

ba0006oc1 | (1) | ICCBH2017

NBAS variants causing a novel form of inherited bone fragility

Balasubramanian Meena , Hurst Jane , DeVile Catherine , Bishop Nick , Arundel Paul , Offiah Amaka , Pollitt Rebecca , Hughes David , Longman Dasa , Caceres Javier , Skerry Tim

Background: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1/15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcomes.Methodology and results: Trio whole exome sequencing in patients with OI identified, in two patients, compound heterozygous mutations in NBAS</...