Ng, Y. S., Alston, C. L., Diodato, D., Morris, A. D., Ulrick, N., Kmoch, S., Houštěk, J., 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., ... McFarland, R. (2016). The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. Journal of Medical Genetics, 53(11), 768-775. https://doi.org/10.1136/jmedgenet-2016-103910
Ng, YS, Alston, CL, Diodato, D, Morris, AD, Ulrick, N, Kmoch, S, Houštěk, J, Martinelli, D, Haghighi, A, Atiq, M, Gamero, MA, Garcia-Martinez, E, Kratochvílová, 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, A-M, Østergaard, E, Vanderver, A, Goldstein, A, Vogt, J, Taylor, RW & McFarland, R 2016, 'The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease', Journal of Medical Genetics, vol. 53, no. 11, pp. 768-775. https://doi.org/10.1136/jmedgenet-2016-103910
@article{f9e9de0a2deb4f11afb7dc94d8af3855,
title = "The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease",
abstract = "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.",
keywords = "Journal Article",
author = "Ng, {Yi Shiau} and Alston, {Charlotte L} and Daria Diodato and Morris, {Andrew D} and Nicole Ulrick and Stanislav Kmoch and Josef Hou{\v s}t{\v e}k and Diego Martinelli and Alireza Haghighi and Mehnaz Atiq and Gamero, {Montserrat Anton} and Elena Garcia-Martinez and Hana Kratochv{\'i}lov{\'a} and Saikat Santra and Brown, {Ruth M} and Brown, {Garry K} and Nicola Ragge and Ahmad Monavari and Karen Pysden and Kirstine Ravn and Casey, {Jillian P} and Arif Khan and Anupam Chakrapani and Grace Vassallo and Cas Simons and Karl McKeever and Siobhan O'Sullivan and Anne-Marie Childs and Elsebet {\O}stergaard and Adeline Vanderver and Amy Goldstein and Julie Vogt and Taylor, {Robert W} and Robert McFarland",
note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/",
year = "2016",
month = nov,
day = "1",
doi = "10.1136/jmedgenet-2016-103910",
language = "English",
volume = "53",
pages = "768--775",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "B M J Group",
number = "11",
}
TY - JOUR
T1 - The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease
AU - Ng, Yi Shiau
AU - Alston, Charlotte L
AU - Diodato, Daria
AU - Morris, Andrew D
AU - Ulrick, Nicole
AU - Kmoch, Stanislav
AU - Houštěk, Josef
AU - Martinelli, Diego
AU - Haghighi, Alireza
AU - Atiq, Mehnaz
AU - Gamero, Montserrat Anton
AU - Garcia-Martinez, Elena
AU - Kratochvílová, Hana
AU - Santra, Saikat
AU - Brown, Ruth M
AU - Brown, Garry K
AU - Ragge, Nicola
AU - Monavari, Ahmad
AU - Pysden, Karen
AU - Ravn, Kirstine
AU - Casey, Jillian P
AU - Khan, Arif
AU - Chakrapani, Anupam
AU - Vassallo, Grace
AU - Simons, Cas
AU - McKeever, Karl
AU - O'Sullivan, Siobhan
AU - Childs, Anne-Marie
AU - Østergaard, Elsebet
AU - Vanderver, Adeline
AU - Goldstein, Amy
AU - Vogt, Julie
AU - Taylor, Robert W
AU - McFarland, Robert
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
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.
KW - Journal Article
U2 - 10.1136/jmedgenet-2016-103910
DO - 10.1136/jmedgenet-2016-103910
M3 - Journal article
C2 - 27412952
SN - 0022-2593
VL - 53
SP - 768
EP - 775
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 11
ER -
