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

0469548 - FGÚ 2017 RIV GB eng J - Journal Article
Ng, Y. S. - Alston, Ch. L. - Diodato, D. - Morris, A. A. - Ulrick, N. - Kmoch, S. - Houštěk, Josef - Martinelli, D. - Haghighi, A. - Atiq, M. - Gamero, M. A. - Garcia-Martinez, E. - Kratochvílová, H. - Santra, S. - Brown, R. M. - Brown, G. K. - Ragge, N. - Monavari, A. - Pysden, K. - Ravn, K. - Casey, J. P. - Khan, A. - Chakrapani, A. - Vassallo, G. - Simons, C. - McKeever, K. - O´Sullivan, S. - Childs, A.-M. - Ostergaard, E. - Vanderver, A. - Goldstein, A. - Vogt, J. - Taylor, R. W. - McFarland, R.
The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease.
Journal of Medical Genetics. Roč. 53, č. 11 (2016), s. 768-775. ISSN 0022-2593. E-ISSN 1468-6244
R&D Projects: GA ČR(CZ) GB14-36804G
Institutional support: RVO:67985823
Keywords : congenital sensorineural deafness * lactic acidosis * mitochondrial respiratory chain deficiencies * prognosis * renal disease
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.451, year: 2016

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. We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants. 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. We can conclude that 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.
Permanent Link: http://hdl.handle.net/11104/0267352