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Biomedicines
Special Issues
Rare Genetic Diseases: From Pathophysiology to Novel Therapeutic Approaches
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Rare Genetic Diseases: From Pathophysiology to Novel Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 7295

Special Issue Editor

Dr. Doris Hendig

E-Mail Website
Guest Editor
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
Interests: Pseudoxanthoma elasticum; extracellular matrix remodeling; rare genetic diseases; pathomechanisms and biomarkers for fibrosis and soft tissue calcification; genetic modifiers

Special Issue Information

Dear Colleagues,

Studies on rare genetic diseases can help to get a better understanding of various molecular mechanisms and the development of novel therapeutic approaches even for disorders that are more common. This Special Issue will focus on the pathophysiology of rare genetic disorders, such as Pseudoxanthoma elasticum (PXE) or related disorders. For instance, mutations in the ATP-binding cassette sub-family C member 6 (ABCC6) gene are the cause of PXE. The disease is clinically characterized by ectopic calcification and degradation of elastic fibers in skin, Bruch’s membrane in the retina and blood vessels. Moreover, PXE shares molecular characteristics with premature aging diseases. Therefore, identification of pathomechanisms in PXE may consequently uncover pathomechanistics underlying disorders that are more common. Although much knowledge on the pathophysiology of PXE and ABCC6 has been gathered in the last two decades, we still do not know the primary pathomechanisms leading to its manifestation, as well as the physiological function of the encoded transporter protein ABCC6. Different therapeutic approaches have reached clinical studies, but none of them have been able to thoroughly prevent or cure PXE. This Special Issue aims to present an update on the basic insights into the pathophysiology along with novel aspects of the clinical presentation and diagnostics as well as therapeutic approaches of rare genetic diseases, such as PXE or others. We invite authors working in the field to submit original research articles as well as reviews fitting the scope of this Special Issue.

Dr. Doris Hendig
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rare genetic disorders
  • Pseudoxanthoma elasticum
  • PXE
  • soft tissue calcification
  • ABCC6
  • elastic fiber
  • extracellular matrix remodeling
  • aging
  • sterile inflammation
  • metabolic disease
  • rare genetic disorders

Published Papers (2 papers)

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Research

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14 pages, 5061 KiB  
Article
The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3
by Andreas Brodehl, Carsten Hain, Franziska Flottmann, Sandra Ratnavadivel, Anna Gaertner, Bärbel Klauke, Jörn Kalinowski, Hermann Körperich, Jan Gummert, Lech Paluszkiewicz, Marcus-André Deutsch and Hendrik Milting
Biomedicines 2021, 9(10), 1400; https://doi.org/10.3390/biomedicines9101400 - 5 Oct 2021
Cited by 16 | Viewed by 2433
Abstract
Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects [...] Read more.
Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES-c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases. Full article
(This article belongs to the Special Issue Rare Genetic Diseases: From Pathophysiology to Novel Therapeutic Approaches)
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Review

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36 pages, 503 KiB  
Review
Therapy of Pseudoxanthoma Elasticum: Current Knowledge and Future Perspectives
by Max Jonathan Stumpf, Nadjib Schahab, Georg Nickenig, Dirk Skowasch and Christian Alexander Schaefer
Biomedicines 2021, 9(12), 1895; https://doi.org/10.3390/biomedicines9121895 - 13 Dec 2021
Cited by 12 | Viewed by 4345
Abstract
Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease with an estimated prevalence of between 1 per 25,000 and 56,000. Its main hallmarks are characteristic skin lesions, development of choroidal neovascularization, and early-onset arterial calcification accompanied by a severe reduction in quality-of-life. Underlying [...] Read more.
Pseudoxanthoma elasticum (PXE) is a rare, genetic, metabolic disease with an estimated prevalence of between 1 per 25,000 and 56,000. Its main hallmarks are characteristic skin lesions, development of choroidal neovascularization, and early-onset arterial calcification accompanied by a severe reduction in quality-of-life. Underlying the pathology are recessively transmitted pathogenic variants of the ABCC6 gene, which results in a deficiency of ABCC6 protein. This results in reduced levels of peripheral pyrophosphate, a strong inhibitor of peripheral calcification, but also dysregulation of blood lipids. Although various treatment options have emerged during the last 20 years, many are either already outdated or not yet ready to be applied generally. Clinical physicians often are left stranded while patients suffer from the consequences of outdated therapies, or feel unrecognized by their attending doctors who may feel uncertain about using new therapeutic approaches or not even know about them. In this review, we summarize the broad spectrum of treatment options for PXE, focusing on currently available clinical options, the latest research and development, and future perspectives. Full article
(This article belongs to the Special Issue Rare Genetic Diseases: From Pathophysiology to Novel Therapeutic Approaches)
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