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The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease

Lookup NU author(s): Dr Yi Ng, Dr Charlotte Alston, Dr Daria Diodato, Professor Robert Taylor, Professor Bobby McFarlandORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.Methods We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.Results We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement.Conclusions The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date.

Publication metadata

Author(s): Ng YS, Alston CL, Diodato D, Morris AA, Ulrick N, Kmoch S, Houstek J, Martinelli D, Haghighi A, Atiq M, Gamero MA, Garcia-Martinez E, Kratochvilova H, Santra S, Brown RM, Brown GK, Ragge N, Monavari A, Pysden K, Ravn K, Casey JP, Khan A, Chakrapani A, Vassallo G, Simons C, McKeever K, O'Sullivan S, Childs AM, Ostergaard E, Vanderver A, Goldstein A, Vogt J, Taylor RW, McFarland R

Publication type: Article

Publication status: Published

Journal: Journal of Medical Genetics

Year: 2016

Volume: 53

Issue: 11

Pages: 768-775

Print publication date: 01/11/2016

Online publication date: 13/07/2016

Acceptance date: 26/05/2016

Date deposited: 20/01/2017

ISSN (print): 0022-2593

ISSN (electronic): 1468-6244

Publisher: BMJ Publishing Group


DOI: 10.1136/jmedgenet-2016-103910


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Funder referenceFunder name
BIOCEV -Biotechnology and Biomedicine Centre of the Academy of Sciences
European Regional Development Fund
Ministry of Health of the Czech Republic
UK NHS Specialised Services and Newcastle upon Tyne Hospitals NHS Foundation Trust
096919Z/11/ZWellcome Trust
14-36804GGrant Agency of the Czech Republic
074454/Z/04/ZWellcome Trust
15-28208AMinistry of Education
CZ.1.05/1.1.00/02.0109Charles University
G0601943Medical Research Council
G0800674Medical Research Council
LH12015Ministry of Education of the Czech Republic
NIHR-HCS-D12-03-04National Institute for Health Research (NIHR)
PRVOUK-P24/LF1/3Charles University