RT Journal Article
T1 The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease
A1 Ng, Yi Shiau
A1 Alston, Charlotte L.
A1 Diodato, Daria
A1 Morris, Andrew A.
A1 Ulrick, Nicole
A1 Kmoch, Stanislav
A1 Houstek, Josef
A1 Martinelli, Diego
A1 Haghighi, Alireza
A1 Atiq, Mehnaz
A1 Gamero, Montserrat Anton
A1 Garcia-Martinez, Elena
A1 Kratochvilova, Hana
A1 Santra, Saikat
A1 Brown, Ruth M.
A1 Brown, Garry K.
A1 Ragge, Nicola
A1 Monavari, Ahmad
A1 Pysden, Karen
A1 Ravn, Kirstine
A1 Casey, Jillian P.
A1 Khan, Arif
A1 Chakrapani, Anupam
A1 Vassallo, Grace
A1 Simons, Cas
A1 McKeever, Karl
A1 O'Sullivan, Siobhan
A1 Childs, Anne-Marie
A1 Ostergaard, Elsebet
A1 Vanderver, Adeline
A1 Goldstein, Amy
A1 Vogt, Julie
A1 Taylor, Robert W.
A1 McFarland, Robert
K1 Complex deficiencies
K1 Rmnd1 mutation
K1 Renal-failure
K1 Encephaloneuromyopathy
K1 Translation
K1 Defect
AB 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.
PB Bmj publishing group
SN 0022-2593
YR 2016
FD 2016-11-01
LK http://hdl.handle.net/10668/19038
UL http://hdl.handle.net/10668/19038
LA en
DS RISalud
RD Apr 8, 2025