Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD
Despite the knowledge of the main mechanisms involved in facioscapulohumeral muscular dystrophy (FSHD), the high heterogeneity and variable penetrance of the disease complicate the diagnosis, characterization and genotype–phenotype correlation of patients and families, raising the need for further r...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/17/2687 |
| _version_ | 1797495943802650624 |
|---|---|
| author | Valerio Caputo Domenica Megalizzi Carlo Fabrizio Andrea Termine Luca Colantoni Carlo Caltagirone Emiliano Giardina Raffaella Cascella Claudia Strafella |
| author_facet | Valerio Caputo Domenica Megalizzi Carlo Fabrizio Andrea Termine Luca Colantoni Carlo Caltagirone Emiliano Giardina Raffaella Cascella Claudia Strafella |
| author_sort | Valerio Caputo |
| collection | DOAJ |
| description | Despite the knowledge of the main mechanisms involved in facioscapulohumeral muscular dystrophy (FSHD), the high heterogeneity and variable penetrance of the disease complicate the diagnosis, characterization and genotype–phenotype correlation of patients and families, raising the need for further research and data. Thus, the present review provides an update of the main molecular aspects underlying the complex architecture of FSHD, including the genetic factors (related to <i>D4Z4</i> repeated units and FSHD-associated genes), epigenetic elements (<i>D4Z4</i> methylation status, non-coding RNAs and high-order chromatin interactions) and gene expression profiles (FSHD transcriptome signatures both at bulk tissue and single-cell level). In addition, the review will also describe the methods currently available for investigating the above-mentioned features and how the resulting data may be combined with artificial-intelligence-based pipelines, with the purpose of developing a multifunctional tool tailored to enhancing the knowledge of disease pathophysiology and progression and fostering the research for novel treatment strategies, as well as clinically useful biomarkers. In conclusion, the present review highlights how FSHD should be regarded as a disease characterized by a molecular spectrum of genetic and epigenetic factors, whose alteration plays a differential role in <i>DUX4</i> repression and, subsequently, contributes to determining the FSHD phenotype. |
| first_indexed | 2024-03-10T01:56:43Z |
| format | Article |
| id | doaj.art-45c5732fc8d74d508a9ad8c96d7875a5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:56:43Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-45c5732fc8d74d508a9ad8c96d7875a52023-11-23T12:55:12ZengMDPI AGCells2073-44092022-08-011117268710.3390/cells11172687Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHDValerio Caputo0Domenica Megalizzi1Carlo Fabrizio2Andrea Termine3Luca Colantoni4Carlo Caltagirone5Emiliano Giardina6Raffaella Cascella7Claudia Strafella8Genomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyGenomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyData Science Unit, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyData Science Unit, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyGenomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyDepartment of Clinical and Behavorial Neurology, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyGenomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyGenomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyGenomic Medicine Laboratory-UILDM, Santa Lucia Foundation IRCCS, 00179 Rome, ItalyDespite the knowledge of the main mechanisms involved in facioscapulohumeral muscular dystrophy (FSHD), the high heterogeneity and variable penetrance of the disease complicate the diagnosis, characterization and genotype–phenotype correlation of patients and families, raising the need for further research and data. Thus, the present review provides an update of the main molecular aspects underlying the complex architecture of FSHD, including the genetic factors (related to <i>D4Z4</i> repeated units and FSHD-associated genes), epigenetic elements (<i>D4Z4</i> methylation status, non-coding RNAs and high-order chromatin interactions) and gene expression profiles (FSHD transcriptome signatures both at bulk tissue and single-cell level). In addition, the review will also describe the methods currently available for investigating the above-mentioned features and how the resulting data may be combined with artificial-intelligence-based pipelines, with the purpose of developing a multifunctional tool tailored to enhancing the knowledge of disease pathophysiology and progression and fostering the research for novel treatment strategies, as well as clinically useful biomarkers. In conclusion, the present review highlights how FSHD should be regarded as a disease characterized by a molecular spectrum of genetic and epigenetic factors, whose alteration plays a differential role in <i>DUX4</i> repression and, subsequently, contributes to determining the FSHD phenotype.https://www.mdpi.com/2073-4409/11/17/2687FSHD<i>DUX4</i>muscular distrophygenomicstranscriptomics(epi)genetics |
| spellingShingle | Valerio Caputo Domenica Megalizzi Carlo Fabrizio Andrea Termine Luca Colantoni Carlo Caltagirone Emiliano Giardina Raffaella Cascella Claudia Strafella Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD Cells FSHD <i>DUX4</i> muscular distrophy genomics transcriptomics (epi)genetics |
| title | Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD |
| title_full | Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD |
| title_fullStr | Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD |
| title_full_unstemmed | Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD |
| title_short | Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD |
| title_sort | update on the molecular aspects and methods underlying the complex architecture of fshd |
| topic | FSHD <i>DUX4</i> muscular distrophy genomics transcriptomics (epi)genetics |
| url | https://www.mdpi.com/2073-4409/11/17/2687 |
| work_keys_str_mv | AT valeriocaputo updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT domenicamegalizzi updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT carlofabrizio updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT andreatermine updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT lucacolantoni updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT carlocaltagirone updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT emilianogiardina updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT raffaellacascella updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd AT claudiastrafella updateonthemolecularaspectsandmethodsunderlyingthecomplexarchitectureoffshd |