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Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature
OBJECTIVE: This study analyzed eight Chinese short stature children with aggrecan deficiency, and aimed to investigate potential genotype–phenotype correlations, differences in clinical characteristics between the Chinese and the Western populations, and effectiveness of recombinant human growth hor...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649928/ https://www.ncbi.nlm.nih.gov/pubmed/36387899 http://dx.doi.org/10.3389/fendo.2022.1015954 |
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author | Deng, Shuyun Hou, Lele Xia, Dan Li, Xiaojuan Peng, Xiaofang Xiao, Xiaoqin Zhang, Jieming Meng, Zhe Zhang, Lina Ouyang, Nengtai Liang, Liyang |
author_facet | Deng, Shuyun Hou, Lele Xia, Dan Li, Xiaojuan Peng, Xiaofang Xiao, Xiaoqin Zhang, Jieming Meng, Zhe Zhang, Lina Ouyang, Nengtai Liang, Liyang |
author_sort | Deng, Shuyun |
collection | PubMed |
description | OBJECTIVE: This study analyzed eight Chinese short stature children with aggrecan deficiency, and aimed to investigate potential genotype–phenotype correlations, differences in clinical characteristics between the Chinese and the Western populations, and effectiveness of recombinant human growth hormone therapy in patients with ACAN variants through a review of the literature. METHODS: Pediatric short stature patients with ACAN heterozygous variants were identified using whole-exome sequencing. Subsequently, a literature review was carried out to summarize the clinical features, genetic findings, and efficacy of growth-promoting therapy in patients with ACAN variants. RESULTS: We identified seven novel ACAN mutations and one recurrent variant. Patients in our center manifested with short stature (average height SDS: -3.30 ± 0.85) with slight dysmorphic characteristics. The prevalence of dysmorphic features in the Chinese populations is significantly lower than that in the Western populations. Meanwhile, only 24.24% of aggrecan-deficient Chinese children showed significantly advanced bone age (BA). Promising therapeutic benefits were seen in the patients who received growth-promoting treatment, with an increase in growth velocity from 4.52 ± 1.00 cm/year to 8.03 ± 1.16 cm/year. CONCLUSION: This study further expanded the variation spectrum of the ACAN gene and demonstrated that Chinese children with short stature who carried ACAN heterozygous variants exhibited early growth cessation, which may remain unnoticed by clinicians as most of these children had very mild dysmorphic characteristics and showed BA that was consistent with the chronological age. Genetic testing may help in the diagnosis. |
format | Online Article Text |
id | pubmed-9649928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96499282022-11-15 Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature Deng, Shuyun Hou, Lele Xia, Dan Li, Xiaojuan Peng, Xiaofang Xiao, Xiaoqin Zhang, Jieming Meng, Zhe Zhang, Lina Ouyang, Nengtai Liang, Liyang Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: This study analyzed eight Chinese short stature children with aggrecan deficiency, and aimed to investigate potential genotype–phenotype correlations, differences in clinical characteristics between the Chinese and the Western populations, and effectiveness of recombinant human growth hormone therapy in patients with ACAN variants through a review of the literature. METHODS: Pediatric short stature patients with ACAN heterozygous variants were identified using whole-exome sequencing. Subsequently, a literature review was carried out to summarize the clinical features, genetic findings, and efficacy of growth-promoting therapy in patients with ACAN variants. RESULTS: We identified seven novel ACAN mutations and one recurrent variant. Patients in our center manifested with short stature (average height SDS: -3.30 ± 0.85) with slight dysmorphic characteristics. The prevalence of dysmorphic features in the Chinese populations is significantly lower than that in the Western populations. Meanwhile, only 24.24% of aggrecan-deficient Chinese children showed significantly advanced bone age (BA). Promising therapeutic benefits were seen in the patients who received growth-promoting treatment, with an increase in growth velocity from 4.52 ± 1.00 cm/year to 8.03 ± 1.16 cm/year. CONCLUSION: This study further expanded the variation spectrum of the ACAN gene and demonstrated that Chinese children with short stature who carried ACAN heterozygous variants exhibited early growth cessation, which may remain unnoticed by clinicians as most of these children had very mild dysmorphic characteristics and showed BA that was consistent with the chronological age. Genetic testing may help in the diagnosis. Frontiers Media S.A. 2022-10-28 /pmc/articles/PMC9649928/ /pubmed/36387899 http://dx.doi.org/10.3389/fendo.2022.1015954 Text en Copyright © 2022 Deng, Hou, Xia, Li, Peng, Xiao, Zhang, Meng, Zhang, Ouyang and Liang 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 | Endocrinology Deng, Shuyun Hou, Lele Xia, Dan Li, Xiaojuan Peng, Xiaofang Xiao, Xiaoqin Zhang, Jieming Meng, Zhe Zhang, Lina Ouyang, Nengtai Liang, Liyang Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title | Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title_full | Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title_fullStr | Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title_full_unstemmed | Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title_short | Description of the molecular and phenotypic spectrum in Chinese patients with aggrecan deficiency: Novel ACAN heterozygous variants in eight Chinese children and a review of the literature |
title_sort | description of the molecular and phenotypic spectrum in chinese patients with aggrecan deficiency: novel acan heterozygous variants in eight chinese children and a review of the literature |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649928/ https://www.ncbi.nlm.nih.gov/pubmed/36387899 http://dx.doi.org/10.3389/fendo.2022.1015954 |
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