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Variable expressivity in a family with an aggrecanopathy

BACKGROUND: Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic vari...

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Autores principales: Denis, Antoine, Chergui, Sami, Basalom, Shuaa, Campeau, Philippe M., Janelle, Chantal, Pauyo, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801139/
https://www.ncbi.nlm.nih.gov/pubmed/34894100
http://dx.doi.org/10.1002/mgg3.1773
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author Denis, Antoine
Chergui, Sami
Basalom, Shuaa
Campeau, Philippe M.
Janelle, Chantal
Pauyo, Thierry
author_facet Denis, Antoine
Chergui, Sami
Basalom, Shuaa
Campeau, Philippe M.
Janelle, Chantal
Pauyo, Thierry
author_sort Denis, Antoine
collection PubMed
description BACKGROUND: Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic variants in the gene encoding Aggrecan; ACAN. Aggrecan, a proteoglycan, is an essential component of the articular and growth plate cartilage. METHODS: Herein, we report three individuals from one family; the proband who presented with short stature, a lower limb bone exostosis, and bilateral knee and elbow OCD at the age of 13 years old. His twin brother presented with isolated short stature and his father with short stature and lumbar disc herniation. RESULTS: Next‐generation sequencing of the ACAN gene in the proband identified a frameshift variant which is also present in the brother and father with short stature. The proband was treated surgically with bilateral elbow microfracture, after the failure of conservative therapy. CONCLUSION: To the best of our knowledge, this is the first patient with an aggrecanopathy who presents with osteochondritis dissecans due to a frameshift variant. This family presents with variable expressivity which might be attributed to modifier genes.
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spelling pubmed-88011392022-02-04 Variable expressivity in a family with an aggrecanopathy Denis, Antoine Chergui, Sami Basalom, Shuaa Campeau, Philippe M. Janelle, Chantal Pauyo, Thierry Mol Genet Genomic Med Original Articles BACKGROUND: Osteochondritis dissecans is a condition wherein there is a subchondral bone lesion that causes pain, inflammation, and cartilage damage. Dominant Familial Osteochondritis Dissecans is a rare and severe form of osteochondritis dissecans (OCD). It is caused by heterozygous pathogenic variants in the gene encoding Aggrecan; ACAN. Aggrecan, a proteoglycan, is an essential component of the articular and growth plate cartilage. METHODS: Herein, we report three individuals from one family; the proband who presented with short stature, a lower limb bone exostosis, and bilateral knee and elbow OCD at the age of 13 years old. His twin brother presented with isolated short stature and his father with short stature and lumbar disc herniation. RESULTS: Next‐generation sequencing of the ACAN gene in the proband identified a frameshift variant which is also present in the brother and father with short stature. The proband was treated surgically with bilateral elbow microfracture, after the failure of conservative therapy. CONCLUSION: To the best of our knowledge, this is the first patient with an aggrecanopathy who presents with osteochondritis dissecans due to a frameshift variant. This family presents with variable expressivity which might be attributed to modifier genes. John Wiley and Sons Inc. 2021-12-10 /pmc/articles/PMC8801139/ /pubmed/34894100 http://dx.doi.org/10.1002/mgg3.1773 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Denis, Antoine
Chergui, Sami
Basalom, Shuaa
Campeau, Philippe M.
Janelle, Chantal
Pauyo, Thierry
Variable expressivity in a family with an aggrecanopathy
title Variable expressivity in a family with an aggrecanopathy
title_full Variable expressivity in a family with an aggrecanopathy
title_fullStr Variable expressivity in a family with an aggrecanopathy
title_full_unstemmed Variable expressivity in a family with an aggrecanopathy
title_short Variable expressivity in a family with an aggrecanopathy
title_sort variable expressivity in a family with an aggrecanopathy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801139/
https://www.ncbi.nlm.nih.gov/pubmed/34894100
http://dx.doi.org/10.1002/mgg3.1773
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