Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784836900026056704 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9690861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT klinebriannal integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT jaillardsylvie integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT bellkatrinam integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT bakhshalizadehshabnam integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT robevskagorjana integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT vandenbergenjocelyn integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT dulonjerome integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT ayerskatiel integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT christodouloujohn integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT tchanmichelc integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT tourainephilippe integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT sinclairandrewh integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency AT tuckerelenaj integralroleofthemitochondrialribosomeinsupportingovarianfunctionmrps7variantsinsyndromicprematureovarianinsufficiency |