Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency

S Bakhshalizadeh; DH Hock; NA Siddall; BL Kline; R Sreenivasan; KM Bell; F Casagranda; S Kamalanathan; J Sahoo; N Narayanan; D Naik; V Suryadevara; AG Compton; SSC Amarasekera; R Kapoor; S Jaillard; A Simpson; G Robevska; J van den Bergen; S Pachernegg; KL Ayers; DR Thorburn; DA Stroud; GR Hime; AH Sinclair; EJ Tucker

Journal article

Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency

S Bakhshalizadeh, DH Hock, NA Siddall, BL Kline, R Sreenivasan, KM Bell, F Casagranda, S Kamalanathan, J Sahoo, N Narayanan, D Naik, V Suryadevara, AG Compton, SSC Amarasekera, R Kapoor, S Jaillard, A Simpson, G Robevska, J van den Bergen, S Pachernegg Show all

Human Genetics | Published : 2023

DOI: 10.1007/s00439-023-02563-z

Abstract

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitoc..

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University of Melbourne Researchers

Daniella Hock Author

Nicole Siddall Author

Alison G Compton Author

Svenja Pachernegg Author

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Grants

Awarded by Mito Foundation

Funding Acknowledgements

This work was supported by a National Health and Medical Research Council (NHMRC) program Grant (1074258 to Andrew H. Sinclair), NHMRC Grants (1140906 to David A. Stroud, 1164479 to David R. Thorburn), NHMRC fellowships (1054432 to Elena J. Tucker, 1126995 to Rajini Sreenivasan, 2009732 to David A. Stroud, 1155244 to David R. Thorburn, 1062854 to Andrew H. Sinclair), a Suzi Carp postdoctoral scholarship (to Elena J. Tucker), a CHU Rennes Grant (Appel a Projects Innovations 2019 to Sylvie Jaillard), US Department of Defense Congressionally Directed Medical Research Program Grant (PR170396 to David R. Thorburn), an Australian Mito Foundation incubator Grants (to Elena J. Tucker), Melbourne International Research Scholarships (Shabnam Bakhshalizadeh, Daniella H. Hock) and the Mito Foundation PhD Top-up Scholarship (Daniella H. Hock). The research conducted at the Murdoch Children's Research Institute was supported by the Victorian government's operational infrastructure support program. We acknowledge the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for the provision of instrumentation, training, and technical support.