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Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with...

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Autores principales: Hasegawa, Kosei, Futagawa, Natsuko, Ago, Yuko, Miyahara, Hiroyuki, Harada, Daisuke, Miyazawa, Mari, Yoshimoto, Junko, Baba, Kenji, Moriwake, Tadashi, Tanaka, Hiroyuki, Tsukahara, Hirokazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society for Pediatric Endocrinology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568574/
https://www.ncbi.nlm.nih.gov/pubmed/37842142
http://dx.doi.org/10.1297/cpe.2023-0035
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author Hasegawa, Kosei
Futagawa, Natsuko
Ago, Yuko
Miyahara, Hiroyuki
Harada, Daisuke
Miyazawa, Mari
Yoshimoto, Junko
Baba, Kenji
Moriwake, Tadashi
Tanaka, Hiroyuki
Tsukahara, Hirokazu
author_facet Hasegawa, Kosei
Futagawa, Natsuko
Ago, Yuko
Miyahara, Hiroyuki
Harada, Daisuke
Miyazawa, Mari
Yoshimoto, Junko
Baba, Kenji
Moriwake, Tadashi
Tanaka, Hiroyuki
Tsukahara, Hirokazu
author_sort Hasegawa, Kosei
collection PubMed
description Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.
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spelling pubmed-105685742023-10-13 Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods Hasegawa, Kosei Futagawa, Natsuko Ago, Yuko Miyahara, Hiroyuki Harada, Daisuke Miyazawa, Mari Yoshimoto, Junko Baba, Kenji Moriwake, Tadashi Tanaka, Hiroyuki Tsukahara, Hirokazu Clin Pediatr Endocrinol Original Article Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease. The Japanese Society for Pediatric Endocrinology 2023-09-16 2023 /pmc/articles/PMC10568574/ /pubmed/37842142 http://dx.doi.org/10.1297/cpe.2023-0035 Text en 2023©The Japanese Society for Pediatric Endocrinology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Original Article
Hasegawa, Kosei
Futagawa, Natsuko
Ago, Yuko
Miyahara, Hiroyuki
Harada, Daisuke
Miyazawa, Mari
Yoshimoto, Junko
Baba, Kenji
Moriwake, Tadashi
Tanaka, Hiroyuki
Tsukahara, Hirokazu
Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title_full Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title_fullStr Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title_full_unstemmed Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title_short Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
title_sort novel and recurrent comp gene variants in five japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568574/
https://www.ncbi.nlm.nih.gov/pubmed/37842142
http://dx.doi.org/10.1297/cpe.2023-0035
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