Calcified Tissue International

, Volume 103, Issue 3, pp 353–358 | Cite as

Autosomal Recessive Osteogenesis Imperfecta Caused by a Novel Homozygous COL1A2 Mutation

  • Alice CostantiniEmail author
  • Symeon Tournis
  • Anders Kämpe
  • Noor Ul Ain
  • Fulya Taylan
  • Artemis Doulgeraki
  • Outi Mäkitie
Case Reports


Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle bones and extraskeletal manifestations. The disease phenotype varies greatly. Most commonly, OI arises from monoallelic mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal dominant trait. Here, we describe a consanguineous family with autosomal recessive OI caused by a novel homozygous glycine substitution in COL1A2, NM_000089.3: c.604G>A, p.(Gly202Ser), detected by whole-genome sequencing. The index patient is a 31-year-old Greek woman with severe skeletal fragility. She had mild short stature, low bone mineral density of the lumbar spine and blue sclerae. She had sustained multiple long bone and vertebral fractures since childhood and had been treated with bisphosphonates for several years. She also had an affected sister with similar clinical manifestations. Interestingly, the parents and one sister, all carriers of the COL1A2 glycine mutation, did not have manifestations of OI. In summary, we report on autosomal recessive OI caused by a homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal fragility. The mutation carriers lacked OI manifestations. This family further expands the complex genetic spectrum of OI and underscores the importance of genetic evaluation for correct genetic counselling.


Autosomal recessive Type I collagen Osteogenesis imperfecta BMD Fracture 



We would like to thank the Swedish Research Council for the financial support and the Science for Life Laboratory (SciLifeLab) for supplying bioinformatics support.

Author Contributions

Study design: AC, AD, OM. Study conduct: AC, ST, AD. Data collection: AC, ST, AD, OM. Data analysis: AC. Data interpretation: AC, ST, AK, NUA, FT, AD, OM. Drafting manuscript: AC, ST, AD, OM. Revision of manuscript content: all authors. Approval of final version of manuscript: all authors. Responsibility for the integrity of the data: all authors.


The funding was provided by Swedish Research Council.

Compliance with Ethical Standards

Conflict of interest

Alice Costantini, Symeon Tournis, Anders Kämpe, Noor Ul Ain, Fulya Taylan, Artemis Doulgeraki, and Outi Mäkitie declare no conflict of interest.

Human and Animal Rights

All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

A written informed consent was obtained from each participant before inclusion into the study.

Supplementary material

223_2018_414_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular Medicine and Surgery and Center for Molecular MedicineKarolinska InstitutetStockholmSweden
  2. 2.Laboratory for Research of the Musculoskeletal System ‘Th. Garofalidis’, School of Medicine, KAT HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.School of Biological SciencesUniversity of the PunjabLahorePakistan
  4. 4.Department of Bone and Mineral Metabolism, Institute of Child Health“Aghia Sophia” Children’s HospitalAthensGreece
  5. 5.Folkhälsan Institute of GeneticsHelsinkiFinland
  6. 6.Children’s HospitalUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
  7. 7.Department of Clinical GeneticsKarolinska University HospitalStockholmSweden

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