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Molecular Basis of Rare Genetic Diseases
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Molecular Basis of Rare Genetic Diseases

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: 10 September 2024 | Viewed by 1038

Special Issue Editors

Prof. Dr. Paulo Ricardo Gazzola Zen

E-Mail Website
Guest Editor
Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
Interests: rare genetic diseases; epidemiology; genes; molecular basis; genomic medicine; cytogenetics
Special Issues, Collections and Topics in MDPI journals
Dr. Rafaella Mergener

E-Mail Website
Guest Editor Assistant
Graduate Program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
Interests: rare genetic diseases; epidemiology; genes; molecular basis; genomic medicine; cytogenetics

Special Issue Information

Dear Colleagues,

According to the World Health Organization, rare diseases affect 65 out of 100,000 individuals. Around 80% of rare diseases are genetic, and the majority clinically manifest in childhood.

Currently, specific treatment are available for several genetic diseases that improve the patients’ life expectancy and quality and reduce the mortality risk. Knowledge of the molecular basis of rare diseases is important, both for making appropriate diagnoses and for developing specific therapies. In addition, early diagnosis is also important so that specific or supportive therapies can be started as early as possible.

In this Special Issue, we will bring together contributions that help to identify the molecular basis of rare diseases. Review or original articles that address this are welcome. 

Prof. Dr. Paulo Ricardo Gazzola Zen
Guest Editor

Dr. Rafaella Mergener
Guest Editor Assistant

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. Genes 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 diseases
  • genetic disorders
  • whole-exome sequencing
  • genome analysis
  • genes

Published Papers (2 papers)

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Research

15 pages, 1980 KiB  
Article
Deafness DFNB128 Associated with a Recessive Variant of Human MAP3K1 Recapitulates Hearing Loss of Map3k1-Deficient Mice
by Rabia Faridi, Rizwan Yousaf, Sayaka Inagaki, Rafal Olszewski, Shoujun Gu, Robert J. Morell, Elizabeth Wilson, Ying Xia, Tanveer Ahmed Qaiser, Muhammad Rashid, Cristina Fenollar-Ferrer, Michael Hoa, Sheikh Riazuddin and Thomas B. Friedman
Genes 2024, 15(7), 845; https://doi.org/10.3390/genes15070845 - 27 Jun 2024
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Abstract
Deafness in vertebrates is associated with variants of hundreds of genes. Yet, many mutant genes causing rare forms of deafness remain to be discovered. A consanguineous Pakistani family segregating nonsyndromic deafness in two sibships were studied using microarrays and exome sequencing. A 1.2 [...] Read more.
Deafness in vertebrates is associated with variants of hundreds of genes. Yet, many mutant genes causing rare forms of deafness remain to be discovered. A consanguineous Pakistani family segregating nonsyndromic deafness in two sibships were studied using microarrays and exome sequencing. A 1.2 Mb locus (DFNB128) on chromosome 5q11.2 encompassing six genes was identified. In one of the two sibships of this family, a novel homozygous recessive variant NM_005921.2:c.4460G>A p.(Arg1487His) in the kinase domain of MAP3K1 co-segregated with nonsyndromic deafness. There are two previously reported Map3k1-kinase-deficient mouse models that are associated with recessively inherited syndromic deafness. MAP3K1 phosphorylates serine and threonine and functions in a signaling pathway where pathogenic variants of HGF, MET, and GAB1 were previously reported to be associated with human deafness DFNB39, DFNB97, and DFNB26, respectively. Our single-cell transcriptome data of mouse cochlea mRNA show expression of Map3k1 and its signaling partners in several inner ear cell types suggesting a requirement of wild-type MAP3K1 for normal hearing. In contrast to dominant variants of MAP3K1 associated with Disorders of Sex Development 46,XY sex-reversal, our computational modeling of the recessive substitution p.(Arg1487His) predicts a subtle structural alteration in MAP3K1, consistent with the limited phenotype of nonsyndromic deafness. Full article
(This article belongs to the Special Issue Molecular Basis of Rare Genetic Diseases)
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13 pages, 2853 KiB  
Article
Presentation of Rare Phenotypes Associated with the FKBP10 Gene
by Elena S. Merkuryeva, Tatiana V. Markova, Vladimir M. Kenis, Olga E. Agranovich, Ivan M. Dan, Yulia Y. Kotalevskaya, Olga A. Shchagina, Oxana P. Ryzhkova, Sergei S. Fomenko, Elena L. Dadali and Sergey I. Kutsev
Genes 2024, 15(6), 674; https://doi.org/10.3390/genes15060674 - 23 May 2024
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Abstract
Pathogenic variants in the FKBP10 gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. [...] Read more.
Pathogenic variants in the FKBP10 gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. This study analyzed the clinical-genetic characteristics of patients with these conditions, focusing on both known and newly identified FKBP10 variants. We examined data from 15 patients, presenting symptoms of OI and joint contractures. Diagnostic methods included genealogical analysis, clinical assessments, radiography, whole exome sequencing, and direct automated Sanger sequencing. We diagnosed 15 patients with phenotypes due to biallelic FKBP10 variants—4 with OI Type XI, 10 with BS I, and 1 with the AG-like phenotype—demonstrating polymorphism in disease severity. Ten pathogenic FKBP10 variants were identified, including three novel ones, c.1373C>T (p.Pro458Leu), c.21del (p.Pro7fs), and c.831_832insCG (p.Gly278Argfs), and a recurrent variant, c.831dup (p.Gly278Argfs). Variant c.1490G>A (p.Trp497Ter) was found in two unrelated patients, causing OI XI in one and BS I in the other. Additionally, two unrelated patients with BS I and epidermolysis bullosa shared identical homozygous FKBP10 and KRT14 variants. This observation illustrates the diversity of FKBP10-related pathology and the importance of considering the full spectrum of phenotypes in clinical diagnostics. Full article
(This article belongs to the Special Issue Molecular Basis of Rare Genetic Diseases)
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