Autism and heritable bone fragility: a true association?
Open accessAbstract
OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; intelligence is reported to be normal. However, a minority of children seen also show symptomology consistent with an 'Autism Spectrum Disorder'. A joint genetics and psychology research study was undertaken to identify these patients using 'Gold Standard' research tools: Autism Diagnostic Inventory Revised (ADI-R); Autism Diagnostic Observation Schedule (ADOS) and undertake genetic analyses in them. METHOD: = 7 children with autistic traits and severe/complex OI were recruited to the study. The study was set-up to explore whether there was a genetic link between bone fragility and autism in a sub-set of patients with bone fragility identified with autism traits in our complex/severe OI clinic. This was not set-up as a prevalence study but rather an exploration of genetics in association with ADI/ADOS confirmed ASD and bone fragility. ADI& ADOS: Standardised tools were used to confirm autism diagnosis. ADI and ADOS were completed by the Clinical Psychologist; ADI comprises a 93 item semi-structured clinical review with a diagnostic algorithm diagnosing Autism; ADOS is a semi-structured assessment of socialisation, communication and play/imagination which also provides a diagnostic algorithm. EXOME SEQUENCING: In patients recruited, those that fulfilled research criteria for diagnosis of autism using above tools were recruited to trio whole exome sequencing (WES). RESULTS: . CONCLUSIONS: Although, not set out as an objective, we were able to establish that identifying autism had important clinical and social benefits for patients and their families in ensuring access to services, appropriate schooling, increased understanding of behaviour and support. LAY SUMMARY: It is important for clinicians looking after children with brittle bone disease, also referred to as Osteogenesis Imperfecta (OI) to be aware of early features of developmental delay/autistic traits especially with severe forms of OI as the emphasis is on their mobility and bone health. Ensuring appropriate assessment and access to services early-on will enable these patients to achieve their potential. Further investigations of genomics in bone fragility in relation to autism are required and dual diagnosis is essential for high quality clinical and educational provision.
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Ten out of 102 patients with Osteogenesis Imperfecta in a cohort have ASD, while in the general population ASD is estimated at 1 in 100.
“Ten out 102 patients in their cohort have ASD while in the general population ASD is estimated of 1 in 100.”
From Autism, joint hypermobility-related disorders and pain (2018) · cites this paper as [37]
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Cites
Genetic heterogeneity in osteogenesis imperfecta.
Sillence, D. O., Senn, A., & Danks, D. M. (1979) · Journal of Medical Genetics · doi:10.1136/jmg.16.2.101 · Cited by 2,244 · see citing works
Baird, G., Simonoff, E., Pickles, A., Chandler, S., Loucas, T., Meldrum, D., & Charman, T. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69041-7 · Cited by 2,104 · see citing works
Forlino, A., & Marini, J. C. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00728-x · Cited by 972 · see citing works
Osteogenesis Imperfecta Type VI: A Form of Brittle Bone Disease with a Mineralization Defect
Glorieux, F. H., Ward, L. M., Rauch, F., et al. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.1.30 · Cited by 446 · see citing works
Diagnosing Autism: Analyses of Data from the Autism Diagnostic Interview
Lord, C., Pickles, A. R., McLennan, J. D., Rutter, M. L., Bregman, J. D., Folstein, S. E., Fombonne, E. J., Leboyer, M., & Minshew, N. J. (1997) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025873925661 · Cited by 374 · see citing works
Early identification of autism spectrum disorders
Zwaigenbaum, L., Bryson, S., & Garon, N. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.04.004 · Cited by 370 · see citing works
Christiansen, H. E., Schwarze, U., Pyott, S. M., Alswaid, A. F., Balwi, M. A. A., Alrasheed, S., Pepin, M. G., Weis, M. A., Eyre, D. R., & Byers, P. H. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.01.034 · Cited by 352 · see citing works
Alanay, Y., Avaygan, H., Camacho, N., Ütine, G. E., Boduroğlu, K., Aktaş, D., Alikaşifoğlu, M., Tunçbılek, E., Orhan, D., Bakar, F. T., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.022 · Cited by 319 · see citing works
Lapunzina, P. D., Aglan, M., Temtamy, S. A., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.05.016 · Cited by 289 · see citing works
PPIB mutations cause severe osteogenesis imperfecta.
van Dijk, F. V., Nesbitt, I., Zwikstra, E. H., Nikkels, P., Piersma, S., Fratantoni, S. A., Jiménez, C., Huizer, M., Morsman, A. C., Cobben, J., et al. (2009) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.001 · Cited by 283 · see citing works
A Single Recurrent Mutation in the 5′-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V
Cho, T., Lee, K.-E., Lee, S.-K., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.06.005 · Cited by 265 · see citing works
Semler, O., Garbes, L., Keupp, K., Swan, D., Zimmermann, K., Becker, J., Iden, S., Wirth, B., Eysel, P., Koerber, F., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.06.011 · Cited by 241 · see citing works
Martínez‐Glez, V., Valencia, M., Caparros-Martin, J. A., Aglan, M., Temtamy, S. A., Tenorio, J. A., Pulido, V., Lindert, U., Rohrbach, M., Eyre, D. R., et al. (2011) · Human Mutation · doi:10.1002/humu.21647 · Cited by 219 · see citing works
CRTAPandLEPRE1mutations in recessive osteogenesis imperfecta
Baldridge, D., Schwarze, U., Morello, R., Lennington, J., Bertin, T., Pace, J. M., Pepin, M. G., Weis, M., Eyre, D. R., Walsh, J., et al. (2008) · Human Mutation · doi:10.1002/humu.20799 · Cited by 208 · see citing works
Hartikka, H., Mäkitie, O., Männikkö, M., Doria, A. S., Daneman, A., Cole, W. G., Ala‐Kokko, L., & Sochett, E. B. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.050101 · Cited by 204 · see citing works
Mutations in WNT1 are a cause of osteogenesis imperfecta
Fahiminiya, S., Majewski, J., Mort, J. S., Moffatt, P., Glorieux, F. H., & Rauch, F. (2013) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2013-101567 · Cited by 198 · see citing works
Le Couteur, A., Haden, G., Hammal, D., & McConachie, H. (2008) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-007-0403-3 · Cited by 181 · see citing works
Gensure, R. C., Mäkitie, O., Barclay, C., Chan, C., DePalma, S. R., Bastepe, M., Abuzahra, H., Couper, R., Mundlos, S., Sillence, D., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22760 · Cited by 172 · see citing works
Folkestad, L., Hald, J. D., Ersbøll, A. K., Gram, J., Hermann, A. P., Langdahl, B. L., Abrahamsen, B., & Brixen, K. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2920 · Cited by 156 · see citing works
Lindert, U., Cabral, W. A., Ausavarat, S., Tongkobpetch, S., Ludin, K., Barnes, A. M., Yeetong, P., Weis, M., Krabichler, B., Srichomthong, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms11920 · Cited by 146 · see citing works
Shaheen, R., Alazami, A. M., Alshammari, M. J., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101142 · Cited by 145 · see citing works
Recessive Osteogenesis Imperfecta Caused by Missense Mutations in SPARC
Mendoza‐Londono, R., Fahiminiya, S., Majewski, J., Tétreault, M., Nadaf, J., Kannus, P., Sochett, E. B., Howard, A., Stimec, J., Dupuis, L., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.04.021 · Cited by 139 · see citing works
Symoens, S., Malfait, F., D’hondt, S., Callewaert, B. L., Dheedene, A., Steyaert, W., Bächinger, H. P., Paepe, A. D., Kayserili, H., & Coucke, P. J. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-154 · Cited by 126 · see citing works
Bone density in peripubertal boys with Autism Spectrum Disorders
Neumeyer, A. M., Gates, A., Ferrone, C., Lee, H., & Misra, M. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1709-3 · Cited by 91 · see citing works
Brief report: Bone fractures in children and adults with autism spectrum disorders
Neumeyer, A. M., O’Rourke, J. A., Massa, A., Lee, H., Lawson, E. A., McDougle, C. J., & Misra, M. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2228-1 · Cited by 77 · see citing works
Caffey disease: an unlikely collagenopathy
Glorieux, F. H. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25148 · Cited by 68 · see citing works
Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta
Balasubramanian, M., Hurst, J. A., Brown, S., Bishop, N. J., Arundel, P., DeVile, C. J., Pollitt, R. C., Crooks, L., Longman, D., Cáceres, J. F., et al. (2016) · Bone · doi:10.1016/j.bone.2016.10.023 · Cited by 56 · see citing works
Self-citationSkeletal characteristics associated with homozygous and heterozygous WNT1 mutations
Palomo, T., Al‐Jallad, H., Moffatt, P., et al. (2014) · Bone · doi:10.1016/j.bone.2014.06.041 · Cited by 54 · see citing works
WNT1 mutation with recessive osteogenesis imperfecta and profound neurological phenotype
Faqeih, E., Shaheen, R., & Alkuraya, F. S. (2013) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2013-101750 · Cited by 48 · see citing works
Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders
Ekhlaspour, L., Baskaran, C., Reyes, K. J. C., Sokoloff, N. C., Neumeyer, A. M., & Misra, M. (2016) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-016-2871-9 · Cited by 32 · see citing works
Bone microarchitecture in adolescent boys with autism spectrum disorder
Neumeyer, A. M., Sokoloff, N. C., McDonnell, E., Macklin, E. A., McDougle, C. J., & Misra, M. (2017) · Bone · doi:10.1016/j.bone.2017.01.009 · Cited by 25 · see citing works
Bone Accrual in Males with Autism Spectrum Disorder
Neumeyer, A. M., Sokoloff, N. C., McDonnell, E., Macklin, E. A., McDougle, C. J., & Misra, M. (2016) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.10.080 · Cited by 20 · see citing works
Laine, C. M., Koltin, D., Susic, M., et al. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35278 · Cited by 17 · see citing works
Bone Fractures in Children with Autistic Spectrum Disorder
Furlano, R. I., Bloechliger, M., Jick, H., & Meier, C. R. (2014) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000000070 · Cited by 13 · see citing works
Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta
Balasubramanian, M., Cartwright, A., Smith, K., et al. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37431 · Cited by 5 · see citing works
Self-citationEditorial (Thematic Issue: W(e)nt to the Brain: Wnt Signaling in Neurological Disorders)
Tang, S. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140708121037 · Cited by 2 · see citing works
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Research works printed but not linked: 1
- Balasubramanian M. Clinical and Molecular Heterogeneity of Osteogenesis Imperfecta Colloquium Series on Genomic and Molecular Medicine vol. 8 2017 Morgan & Claypool Life Sciences Publishers San Rafael, CA/United States
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Autism, joint hypermobility-related disorders and pain
Baeza-Velasco, C., Cohen, D., Hamonet, C., Vlamynck, E., Diaz, L., Cravero, C., Cappe, E., & Guinchat, V. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00656 · Cited by 78 · see citing works
Sharp, H. E. C., Critchley, H. D., & Eccles, J. A. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i10.805 · Cited by 32 · see citing works
- Authors
- Balasubramanian, M., Jones, R., Milne, E., Marshall, C., Arundel, P., Smith, K., & Bishop, N. J.
- Affiliations
- Sheffield Children's NHS Foundation Trust (GB)
- University of Sheffield (GB)
- Corresponding author
- Balasubramanian, Meena
- Venue
- Bone Reports
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 8
- Pages
- 156-162
- ISSN
- 2352-1872 (ISSN-L)
- PMC
- PMC6020266
- OpenAlex
- W2801095752
- Cited by
- 11
- References
- 36
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bone Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Newlife the Charity for Disabled Children (SG/14-15/05)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- osteogenesis imperfecta, autism spectrum disorder, bone fragility, dual diagnosis, genetic diagnosis, exome sequencing, developmental delay, children, early diagnosis, bone health
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