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Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency

The mitochondrial ribosome is critical to mitochondrial protein synthesis. Defects in both the large and small subunits of the mitochondrial ribosome can cause human disease, including, but not limited to, cardiomyopathy, hypoglycaemia, neurological dysfunction, sensorineural hearing loss and premat...

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Autores principales: Kline, Brianna L., Jaillard, Sylvie, Bell, Katrina M., Bakhshalizadeh, Shabnam, Robevska, Gorjana, van den Bergen, Jocelyn, Dulon, Jérôme, Ayers, Katie L., Christodoulou, John, Tchan, Michel C., Touraine, Philippe, Sinclair, Andrew H., Tucker, Elena J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690861/
https://www.ncbi.nlm.nih.gov/pubmed/36421788
http://dx.doi.org/10.3390/genes13112113
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author Kline, Brianna L.
Jaillard, Sylvie
Bell, Katrina M.
Bakhshalizadeh, Shabnam
Robevska, Gorjana
van den Bergen, Jocelyn
Dulon, Jérôme
Ayers, Katie L.
Christodoulou, John
Tchan, Michel C.
Touraine, Philippe
Sinclair, Andrew H.
Tucker, Elena J.
author_facet Kline, Brianna L.
Jaillard, Sylvie
Bell, Katrina M.
Bakhshalizadeh, Shabnam
Robevska, Gorjana
van den Bergen, Jocelyn
Dulon, Jérôme
Ayers, Katie L.
Christodoulou, John
Tchan, Michel C.
Touraine, Philippe
Sinclair, Andrew H.
Tucker, Elena J.
author_sort Kline, Brianna L.
collection PubMed
description The mitochondrial ribosome is critical to mitochondrial protein synthesis. Defects in both the large and small subunits of the mitochondrial ribosome can cause human disease, including, but not limited to, cardiomyopathy, hypoglycaemia, neurological dysfunction, sensorineural hearing loss and premature ovarian insufficiency (POI). POI is a common cause of infertility, characterised by elevated follicle-stimulating hormone and amenorrhea in women under the age of 40. Here we describe a patient with POI, sensorineural hearing loss and Hashimoto’s disease. The co-occurrence of POI with sensorineural hearing loss indicates Perrault syndrome. Whole exome sequencing identified two compound heterozygous variants in mitochondrial ribosomal protein 7 (MRPS7), c.373A>T/p.(Lys125*) and c.536G>A/p.(Arg179His). Both novel variants are predicted to be pathogenic via in-silico algorithms. Variants in MRPS7 have been described only once in the literature and were identified in sisters, one of whom presented with congenital sensorineural hearing loss and POI, consistent with our patient phenotype. The other affected sister had a more severe disease course and died in early adolescence due to liver and renal failure before the reproductive phenotype was known. This second independent report validates that variants in MRPS7 are a cause of syndromic POI/Perrault syndrome. We present this case and review the current evidence supporting the integral role of the mitochondrial ribosome in supporting ovarian function.
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spelling pubmed-96908612022-11-25 Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency Kline, Brianna L. Jaillard, Sylvie Bell, Katrina M. Bakhshalizadeh, Shabnam Robevska, Gorjana van den Bergen, Jocelyn Dulon, Jérôme Ayers, Katie L. Christodoulou, John Tchan, Michel C. Touraine, Philippe Sinclair, Andrew H. Tucker, Elena J. Genes (Basel) Case Report The mitochondrial ribosome is critical to mitochondrial protein synthesis. Defects in both the large and small subunits of the mitochondrial ribosome can cause human disease, including, but not limited to, cardiomyopathy, hypoglycaemia, neurological dysfunction, sensorineural hearing loss and premature ovarian insufficiency (POI). POI is a common cause of infertility, characterised by elevated follicle-stimulating hormone and amenorrhea in women under the age of 40. Here we describe a patient with POI, sensorineural hearing loss and Hashimoto’s disease. The co-occurrence of POI with sensorineural hearing loss indicates Perrault syndrome. Whole exome sequencing identified two compound heterozygous variants in mitochondrial ribosomal protein 7 (MRPS7), c.373A>T/p.(Lys125*) and c.536G>A/p.(Arg179His). Both novel variants are predicted to be pathogenic via in-silico algorithms. Variants in MRPS7 have been described only once in the literature and were identified in sisters, one of whom presented with congenital sensorineural hearing loss and POI, consistent with our patient phenotype. The other affected sister had a more severe disease course and died in early adolescence due to liver and renal failure before the reproductive phenotype was known. This second independent report validates that variants in MRPS7 are a cause of syndromic POI/Perrault syndrome. We present this case and review the current evidence supporting the integral role of the mitochondrial ribosome in supporting ovarian function. MDPI 2022-11-14 /pmc/articles/PMC9690861/ /pubmed/36421788 http://dx.doi.org/10.3390/genes13112113 Text en © 2022 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 Case Report
Kline, Brianna L.
Jaillard, Sylvie
Bell, Katrina M.
Bakhshalizadeh, Shabnam
Robevska, Gorjana
van den Bergen, Jocelyn
Dulon, Jérôme
Ayers, Katie L.
Christodoulou, John
Tchan, Michel C.
Touraine, Philippe
Sinclair, Andrew H.
Tucker, Elena J.
Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title_full Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title_fullStr Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title_full_unstemmed Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title_short Integral Role of the Mitochondrial Ribosome in Supporting Ovarian Function: MRPS7 Variants in Syndromic Premature Ovarian Insufficiency
title_sort integral role of the mitochondrial ribosome in supporting ovarian function: mrps7 variants in syndromic premature ovarian insufficiency
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690861/
https://www.ncbi.nlm.nih.gov/pubmed/36421788
http://dx.doi.org/10.3390/genes13112113
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