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Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles
Schwartz–Jampel syndrome (SJS) is an autosomal recessive disorder caused by loss-of-function mutations in heparan sulfate proteoglycan 2 (HSPG2), which encodes the core basement membrane protein perlecan. Myotonia is a major criterion for the diagnosis of SJS; however, its evaluation is based solely...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045278/ https://www.ncbi.nlm.nih.gov/pubmed/36979792 http://dx.doi.org/10.3390/biomedicines11030814 |
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author | Yamashita, Yuri Nakada, Satoshi Nakamura, Kyoko Sakurai, Hidetoshi Ohno, Kinji Goto, Tomohide Mabuchi, Yo Akazawa, Chihiro Hattori, Nobutaka Arikawa-Hirasawa, Eri |
author_facet | Yamashita, Yuri Nakada, Satoshi Nakamura, Kyoko Sakurai, Hidetoshi Ohno, Kinji Goto, Tomohide Mabuchi, Yo Akazawa, Chihiro Hattori, Nobutaka Arikawa-Hirasawa, Eri |
author_sort | Yamashita, Yuri |
collection | PubMed |
description | Schwartz–Jampel syndrome (SJS) is an autosomal recessive disorder caused by loss-of-function mutations in heparan sulfate proteoglycan 2 (HSPG2), which encodes the core basement membrane protein perlecan. Myotonia is a major criterion for the diagnosis of SJS; however, its evaluation is based solely on physical examination and can be challenging in neonates and young children. Furthermore, the pathomechanism underlying SJS-related myotonia is not fully understood, and effective treatments for SJS are limited. Here, we established a cellular model of SJS using patient-derived human-induced pluripotent stem cells. This model exhibited hyper-responsiveness to acetylcholine as a result of abnormalities in the perlecan molecule, which were confirmed via comparison of their calcium imaging with calcium imaging of satellite cells derived from Hspg2(−/−)-Tg mice, which exhibit myotonic symptoms similar to SJS symptoms. Therefore, our results confirm the utility of creating cellular models for investigating SJS and their application in evaluating myotonia in clinical cases, while also providing a useful tool for the future screening of SJS therapies. |
format | Online Article Text |
id | pubmed-10045278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100452782023-03-29 Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles Yamashita, Yuri Nakada, Satoshi Nakamura, Kyoko Sakurai, Hidetoshi Ohno, Kinji Goto, Tomohide Mabuchi, Yo Akazawa, Chihiro Hattori, Nobutaka Arikawa-Hirasawa, Eri Biomedicines Article Schwartz–Jampel syndrome (SJS) is an autosomal recessive disorder caused by loss-of-function mutations in heparan sulfate proteoglycan 2 (HSPG2), which encodes the core basement membrane protein perlecan. Myotonia is a major criterion for the diagnosis of SJS; however, its evaluation is based solely on physical examination and can be challenging in neonates and young children. Furthermore, the pathomechanism underlying SJS-related myotonia is not fully understood, and effective treatments for SJS are limited. Here, we established a cellular model of SJS using patient-derived human-induced pluripotent stem cells. This model exhibited hyper-responsiveness to acetylcholine as a result of abnormalities in the perlecan molecule, which were confirmed via comparison of their calcium imaging with calcium imaging of satellite cells derived from Hspg2(−/−)-Tg mice, which exhibit myotonic symptoms similar to SJS symptoms. Therefore, our results confirm the utility of creating cellular models for investigating SJS and their application in evaluating myotonia in clinical cases, while also providing a useful tool for the future screening of SJS therapies. MDPI 2023-03-07 /pmc/articles/PMC10045278/ /pubmed/36979792 http://dx.doi.org/10.3390/biomedicines11030814 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yamashita, Yuri Nakada, Satoshi Nakamura, Kyoko Sakurai, Hidetoshi Ohno, Kinji Goto, Tomohide Mabuchi, Yo Akazawa, Chihiro Hattori, Nobutaka Arikawa-Hirasawa, Eri Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title | Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title_full | Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title_fullStr | Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title_full_unstemmed | Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title_short | Evaluation of Human-Induced Pluripotent Stem Cells Derived from a Patient with Schwartz–Jampel Syndrome Revealed Distinct Hyperexcitability in the Skeletal Muscles |
title_sort | evaluation of human-induced pluripotent stem cells derived from a patient with schwartz–jampel syndrome revealed distinct hyperexcitability in the skeletal muscles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045278/ https://www.ncbi.nlm.nih.gov/pubmed/36979792 http://dx.doi.org/10.3390/biomedicines11030814 |
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