Genetic Research on Monogenic Skin Disorders

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

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 695

Special Issue Editor


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Guest Editor
1. Department of Medical Genetics, University of Szeged, 6720 Szeged, Hungary
2. ELKH-SZTE Functional Clinical Genetics Research Group, Eötvös Loránd Research Network, 6720 Szeged, Hungary
Interests: monogenic skin diseases

Special Issue Information

Dear Colleagues,

The genome programs of the last 15–20 years have fundamentally changed our knowledge of monogenic skin diseases (genodermatosis). Over the past 15 years, our clinical genetic and genomic studies, genotype–phenotype correlations, haplotype analyses and functional studies carried out in these syndromes have greatly contributed to the fast development of this field. Due to these great achievements, a high number of monogenic skin diseases have been newly described and hundreds of disease-causing genes have been identified. These significant results have led to the identification of thousands of pathogenic variants in the investigated diseases. The clarification of the genetic causes of monogenic skin diseases and the elucidation of the mechanisms of these diseases also provided a solid basis for the development of many new therapeutic modalities.

Although the genome programs of the last 15–20 years have expanded our knowledge about monogenic skin diseases, there are still some unelucidated issues: No 1.: Although missing heritability was first suggested in complex diseases, it is a significant phenomenon in rare monogenic diseases as well. The rate of missing heritability varies tremendously within the monogenic diseases, but in general, missing heritability is smaller among monogenic diseases than among complex ones. No 2.: Genodermatoses develop as a consequence of pathogenic variants in the disease-causing genes, but our previous results demonstrated that even carrying the same disease-causing variants can lead to the development of significantly different phenotypes or even to different diseases. Based on the literature data, there are still a relatively high number of rare skin diseases where the inheritance cannot be explained by the investigation of already identified disease-causing genes; therefore, missing heritability is still an issue in these cases. Moreover, patients affected by rare monogenic skin diseases develop diverse phenotypes, which cannot be explained by the identified pathogenic variants of the disease-causing genes.

This Special Issue aims to publish cutting-edge studies, which elucidate missing heritability and high phenotypic diversity in genodermatoses. These investigations may identify further yet unknown disease-causing genes, phenotype-modifier genetic variants, and/or epigenetic abnormalities associated with missing heritability and high phenotypic diversity in genodermatoses. The results of these investigations not only provide novel research data, but also may be extremely useful for the affected patients and thus may further accelerate the development of clinical genetics and genomics.

We are expecting papers that elucidate missing heritability and high phenotypic diversity in genodermatoses. Thus, papers focusing on novel disease-causing genes, novel rare pathogenic variants, novel phenotype-modifier rare or common variants, novel epigenetic alterations, and novel aspects of the disease mechanisms are greatly welcomed. We are not publishing papers on already-published genetic variants or recurrent variants.

Dr. Nikoletta Nagy
Guest Editor

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Keywords

  • genodermatosis
  • monogenic skin diseases
  • phenotypic diversity
  • missing heritability

Published Papers (1 paper)

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7 pages, 2334 KiB  
Case Report
HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases
by María Carmen Martínez-Romero, María Encarnación Hernández-Contreras, Juan Antonio Bafalliu-Vidal, María Barreda-Sánchez, Teresa Martínez-Menchón, Virginia Cabello-Chaves and Encarna Guillén-Navarro
Genes 2024, 15(6), 687; https://doi.org/10.3390/genes15060687 - 26 May 2024
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Abstract
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, [...] Read more.
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling. Full article
(This article belongs to the Special Issue Genetic Research on Monogenic Skin Disorders)
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