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Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement

RMND1 (required for meiotic nuclear division 1 homolog) pathogenic variants are known to cause combined oxidative phosphorylation deficiency (COXPD11), a severe multisystem disorder. In one patient, a homozygous RMND1 pathogenic variant, with an established role in COXPD11, was associated with a Per...

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Autores principales: Oziębło, Dominika, Pazik, Joanna, Stępniak, Iwona, Skarżyński, Henryk, Ołdak, Monika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564844/
https://www.ncbi.nlm.nih.gov/pubmed/32911714
http://dx.doi.org/10.3390/genes11091060
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author Oziębło, Dominika
Pazik, Joanna
Stępniak, Iwona
Skarżyński, Henryk
Ołdak, Monika
author_facet Oziębło, Dominika
Pazik, Joanna
Stępniak, Iwona
Skarżyński, Henryk
Ołdak, Monika
author_sort Oziębło, Dominika
collection PubMed
description RMND1 (required for meiotic nuclear division 1 homolog) pathogenic variants are known to cause combined oxidative phosphorylation deficiency (COXPD11), a severe multisystem disorder. In one patient, a homozygous RMND1 pathogenic variant, with an established role in COXPD11, was associated with a Perrault-like syndrome. We performed a thorough clinical investigation and applied a targeted multigene hearing loss panel to reveal the cause of hearing loss, ovarian dysfunction (two cardinal features of Perrault syndrome) and chronic kidney disease in two adult female siblings. Two compound heterozygous missense variants, c.583G>A (p.Gly195Arg) and c.818A>C (p.Tyr273Ser), not previously associated with disease, were identified in RMND1 in both patients, and their segregation with disease was confirmed in family members. The patients have no neurological or intellectual impairment, and nephrological evaluation predicts a benign course of kidney disease. Our study presents the mildest, so far reported, RMND1-related phenotype and delivers the first independent confirmation that RMND1 is causally involved in the development of Perrault syndrome with renal involvement. This highlights the importance of including RMND1 to the list of Perrault syndrome causative factors and provides new insight into the clinical manifestation of RMND1 deficiency.
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spelling pubmed-75648442020-10-26 Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement Oziębło, Dominika Pazik, Joanna Stępniak, Iwona Skarżyński, Henryk Ołdak, Monika Genes (Basel) Article RMND1 (required for meiotic nuclear division 1 homolog) pathogenic variants are known to cause combined oxidative phosphorylation deficiency (COXPD11), a severe multisystem disorder. In one patient, a homozygous RMND1 pathogenic variant, with an established role in COXPD11, was associated with a Perrault-like syndrome. We performed a thorough clinical investigation and applied a targeted multigene hearing loss panel to reveal the cause of hearing loss, ovarian dysfunction (two cardinal features of Perrault syndrome) and chronic kidney disease in two adult female siblings. Two compound heterozygous missense variants, c.583G>A (p.Gly195Arg) and c.818A>C (p.Tyr273Ser), not previously associated with disease, were identified in RMND1 in both patients, and their segregation with disease was confirmed in family members. The patients have no neurological or intellectual impairment, and nephrological evaluation predicts a benign course of kidney disease. Our study presents the mildest, so far reported, RMND1-related phenotype and delivers the first independent confirmation that RMND1 is causally involved in the development of Perrault syndrome with renal involvement. This highlights the importance of including RMND1 to the list of Perrault syndrome causative factors and provides new insight into the clinical manifestation of RMND1 deficiency. MDPI 2020-09-08 /pmc/articles/PMC7564844/ /pubmed/32911714 http://dx.doi.org/10.3390/genes11091060 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oziębło, Dominika
Pazik, Joanna
Stępniak, Iwona
Skarżyński, Henryk
Ołdak, Monika
Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title_full Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title_fullStr Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title_full_unstemmed Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title_short Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement
title_sort two novel pathogenic variants confirm rmnd1 causative role in perrault syndrome with renal involvement
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564844/
https://www.ncbi.nlm.nih.gov/pubmed/32911714
http://dx.doi.org/10.3390/genes11091060
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