High Bone Mineral Density Osteogenesis Imperfecta in a Family with a Novel Pathogenic Variant in COL1A2

Lara E Graves; Christie-Lee Wall; Julie N Briody; Bruce Bennetts; Karen Wong; Ella Onikul; Andrew Biggin; Craig F Munns

doi:10.1159/000510463

High Bone Mineral Density Osteogenesis Imperfecta in a Family with a Novel Pathogenic Variant in COL1A2

Horm Res Paediatr. 2020;93(4):263-271. doi: 10.1159/000510463. Epub 2020 Sep 11.

Authors

Lara E Graves¹, Christie-Lee Wall², Julie N Briody³, Bruce Bennetts^{4

5

6}, Karen Wong⁴, Ella Onikul⁷, Andrew Biggin^{2

6}, Craig F Munns^{2

6}

Affiliations

¹ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, New South Wales, Australia, lara.graves@health.nsw.gov.au.
² Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
³ Department of Nuclear Medicine, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁴ Molecular Genetics Department, Western Sydney Genetics Program, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁵ Discipline of Genomic Medicine, Children's Hospital at Westmead Clinical School, Westmead, New South Wales, Australia.
⁶ Discipline of Child and Adolescent Health, Children's Hospital at Westmead Clinical School, Westmead, New South Wales, Australia.
⁷ Department of Medical Imaging, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

PMID: 32920552
DOI: 10.1159/000510463

Abstract

Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in COL1A1 or COL1A2 that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected individuals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in COL1A2 c.3356C>T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders.

Keywords: COL1A2; Fractures; High bone mineral density; Osteogenesis imperfecta.

Publication types

Case Reports

MeSH terms

Adolescent
Amino Acid Substitution
Bone Density*
Collagen Type I / genetics*
Collagen Type I / metabolism
Family*
Female
Humans
Male
Mutation, Missense*
Osteogenesis Imperfecta* / genetics
Osteogenesis Imperfecta* / metabolism
Pedigree*

Substances

COL1A2 protein, human
Collagen Type I