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Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome

Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjec...

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Autores principales: Kałużna, Małgorzata, Budny, Bartłomiej, Rabijewski, Michał, Kałużny, Jarosław, Dubiel, Agnieszka, Trofimiuk-Müldner, Małgorzata, Wrotkowska, Elżbieta, Hubalewska-Dydejczyk, Alicja, Ruchała, Marek, Ziemnicka, Katarzyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229512/
https://www.ncbi.nlm.nih.gov/pubmed/34198905
http://dx.doi.org/10.3390/genes12060868
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author Kałużna, Małgorzata
Budny, Bartłomiej
Rabijewski, Michał
Kałużny, Jarosław
Dubiel, Agnieszka
Trofimiuk-Müldner, Małgorzata
Wrotkowska, Elżbieta
Hubalewska-Dydejczyk, Alicja
Ruchała, Marek
Ziemnicka, Katarzyna
author_facet Kałużna, Małgorzata
Budny, Bartłomiej
Rabijewski, Michał
Kałużny, Jarosław
Dubiel, Agnieszka
Trofimiuk-Müldner, Małgorzata
Wrotkowska, Elżbieta
Hubalewska-Dydejczyk, Alicja
Ruchała, Marek
Ziemnicka, Katarzyna
author_sort Kałużna, Małgorzata
collection PubMed
description Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjects (41 males, 5 females; average age: 29 years old). The studied KS patients were screened for defects in a 38-gene panel with next-generation sequencing (NGS) technology. The analysis revealed 27 pathogenic and likely pathogenic (P/LP) variants, and 21 variants of uncertain significance (VUS). The P/LP variants were detected in 20 patients (43.5%). The prevalence of oligogenic P/LP defects in selected genes among KS patients was 26% (12/46), whereas the co-occurrence of other variants was detected in 43% (20 probands). The examined KS patients showed substantial genotypic and phenotypic variability. A marked difference in non-reproductive phenotypes, involving defects in genes responsible for GnRH neuron development/migration and genes contributing to pituitary development and signaling, was observed. A comprehensive gene panel for IHH testing enabled the detection of clinically relevant variants in the majority of KS patients, which makes targeted NGS an effective molecular tool. The significance of oligogenicity and the high incidence of alterations in selected genes should be further elucidated.
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spelling pubmed-82295122021-06-26 Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome Kałużna, Małgorzata Budny, Bartłomiej Rabijewski, Michał Kałużny, Jarosław Dubiel, Agnieszka Trofimiuk-Müldner, Małgorzata Wrotkowska, Elżbieta Hubalewska-Dydejczyk, Alicja Ruchała, Marek Ziemnicka, Katarzyna Genes (Basel) Article Kallmann syndrome (KS) is a combination of isolated hypogonadotropic hypogonadism (IHH) with olfactory dysfunction, representing a heterogeneous disorder with a broad phenotypic spectrum. The genetic background of KS has not yet been fully established. This study was conducted on 46 Polish KS subjects (41 males, 5 females; average age: 29 years old). The studied KS patients were screened for defects in a 38-gene panel with next-generation sequencing (NGS) technology. The analysis revealed 27 pathogenic and likely pathogenic (P/LP) variants, and 21 variants of uncertain significance (VUS). The P/LP variants were detected in 20 patients (43.5%). The prevalence of oligogenic P/LP defects in selected genes among KS patients was 26% (12/46), whereas the co-occurrence of other variants was detected in 43% (20 probands). The examined KS patients showed substantial genotypic and phenotypic variability. A marked difference in non-reproductive phenotypes, involving defects in genes responsible for GnRH neuron development/migration and genes contributing to pituitary development and signaling, was observed. A comprehensive gene panel for IHH testing enabled the detection of clinically relevant variants in the majority of KS patients, which makes targeted NGS an effective molecular tool. The significance of oligogenicity and the high incidence of alterations in selected genes should be further elucidated. MDPI 2021-06-05 /pmc/articles/PMC8229512/ /pubmed/34198905 http://dx.doi.org/10.3390/genes12060868 Text en © 2021 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
Kałużna, Małgorzata
Budny, Bartłomiej
Rabijewski, Michał
Kałużny, Jarosław
Dubiel, Agnieszka
Trofimiuk-Müldner, Małgorzata
Wrotkowska, Elżbieta
Hubalewska-Dydejczyk, Alicja
Ruchała, Marek
Ziemnicka, Katarzyna
Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title_full Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title_fullStr Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title_full_unstemmed Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title_short Defects in GnRH Neuron Migration/Development and Hypothalamic-Pituitary Signaling Impact Clinical Variability of Kallmann Syndrome
title_sort defects in gnrh neuron migration/development and hypothalamic-pituitary signaling impact clinical variability of kallmann syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229512/
https://www.ncbi.nlm.nih.gov/pubmed/34198905
http://dx.doi.org/10.3390/genes12060868
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