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Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature
Short stature is a frequent disorder in the pediatric population and can be caused by multiple factors. In the last few years, the introduction of Next Generation Sequencing (NGS) in the molecular diagnostic workflow led to the discovery of mutations in novel genes causing short stature including he...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397523/ https://www.ncbi.nlm.nih.gov/pubmed/34456977 http://dx.doi.org/10.3389/fgene.2021.708864 |
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author | Mancioppi, Valentina Prodam, Flavia Mellone, Simona Ricotti, Roberta Giglione, Enza Grasso, Nicolino Vurchio, Denise Petri, Antonella Rabbone, Ivana Giordano, Mara Bellone, Simonetta |
author_facet | Mancioppi, Valentina Prodam, Flavia Mellone, Simona Ricotti, Roberta Giglione, Enza Grasso, Nicolino Vurchio, Denise Petri, Antonella Rabbone, Ivana Giordano, Mara Bellone, Simonetta |
author_sort | Mancioppi, Valentina |
collection | PubMed |
description | Short stature is a frequent disorder in the pediatric population and can be caused by multiple factors. In the last few years, the introduction of Next Generation Sequencing (NGS) in the molecular diagnostic workflow led to the discovery of mutations in novel genes causing short stature including heterozygous mutations in ACAN gene. It encodes for aggrecan, a primary proteoglycan component specific for the structure of the cartilage growth plate, articular and intervertebral disc. We report a novel ACAN heterozygous pathogenic variant in a family with idiopathic short stature, early-onset osteoarthritis and osteoarthritis dissecans (SSOAOD). We also performed a literature review summarizing the clinical characteristic of ACAN's patients. The probands are two Caucasian sisters with a family history of short stature and osteoarthritis dissecans. They showed dysmorphic features such as mild midface hypoplasia, brachydactyly and broad thumbs, especially the great toes. The same phenotype was presented in the mother who had had short stature and suffered from intervertebral disc disease. DNA sequencing identified a heterozygous pathogenic variation (c.4390delG p.Val1464Ter) in the sisters, with a maternal inheritance. The nonsense mutation, located on exon 12, results in premature truncation and presumed loss of protein function. In terms of treatment, our patients underwent recombinant human growth hormone replacement therapy, associated with gonadotropin releasing hormone therapy, in order to block early growth cessation and therefore reach a better final height. Our case suggests that SSOAOD ACAN related should be considered in the differential diagnosis of children with autosomal dominant short stature and family history of joints disease. |
format | Online Article Text |
id | pubmed-8397523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83975232021-08-28 Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature Mancioppi, Valentina Prodam, Flavia Mellone, Simona Ricotti, Roberta Giglione, Enza Grasso, Nicolino Vurchio, Denise Petri, Antonella Rabbone, Ivana Giordano, Mara Bellone, Simonetta Front Genet Genetics Short stature is a frequent disorder in the pediatric population and can be caused by multiple factors. In the last few years, the introduction of Next Generation Sequencing (NGS) in the molecular diagnostic workflow led to the discovery of mutations in novel genes causing short stature including heterozygous mutations in ACAN gene. It encodes for aggrecan, a primary proteoglycan component specific for the structure of the cartilage growth plate, articular and intervertebral disc. We report a novel ACAN heterozygous pathogenic variant in a family with idiopathic short stature, early-onset osteoarthritis and osteoarthritis dissecans (SSOAOD). We also performed a literature review summarizing the clinical characteristic of ACAN's patients. The probands are two Caucasian sisters with a family history of short stature and osteoarthritis dissecans. They showed dysmorphic features such as mild midface hypoplasia, brachydactyly and broad thumbs, especially the great toes. The same phenotype was presented in the mother who had had short stature and suffered from intervertebral disc disease. DNA sequencing identified a heterozygous pathogenic variation (c.4390delG p.Val1464Ter) in the sisters, with a maternal inheritance. The nonsense mutation, located on exon 12, results in premature truncation and presumed loss of protein function. In terms of treatment, our patients underwent recombinant human growth hormone replacement therapy, associated with gonadotropin releasing hormone therapy, in order to block early growth cessation and therefore reach a better final height. Our case suggests that SSOAOD ACAN related should be considered in the differential diagnosis of children with autosomal dominant short stature and family history of joints disease. Frontiers Media S.A. 2021-08-12 /pmc/articles/PMC8397523/ /pubmed/34456977 http://dx.doi.org/10.3389/fgene.2021.708864 Text en Copyright © 2021 Mancioppi, Prodam, Mellone, Ricotti, Giglione, Grasso, Vurchio, Petri, Rabbone, Giordano and Bellone. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Mancioppi, Valentina Prodam, Flavia Mellone, Simona Ricotti, Roberta Giglione, Enza Grasso, Nicolino Vurchio, Denise Petri, Antonella Rabbone, Ivana Giordano, Mara Bellone, Simonetta Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title | Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title_full | Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title_fullStr | Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title_full_unstemmed | Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title_short | Retrospective Diagnosis of a Novel ACAN Pathogenic Variant in a Family With Short Stature: A Case Report and Review of the Literature |
title_sort | retrospective diagnosis of a novel acan pathogenic variant in a family with short stature: a case report and review of the literature |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397523/ https://www.ncbi.nlm.nih.gov/pubmed/34456977 http://dx.doi.org/10.3389/fgene.2021.708864 |
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