-
Something wrong with this record ?
The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease
Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, Josef Houštěk, Diego Martinelli, Alireza Haghighi, Mehnaz Atiq, Montserrat Anton Gamero, Elena Garcia-Martinez, Hana Kratochvílová, Saikat Santra,...
Language English Country Great Britain
Document type Research Support, Non-U.S. Gov't, Clinical Study
Grant support
NV15-28208A
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
ProQuest Central
from 1994-01-01 to 6 months ago
Health & Medicine (ProQuest)
from 1994-01-01 to 6 months ago
- Keywords
- RMND1,
- MeSH
- Child MeSH
- Genetic Association Studies MeSH
- Humans MeSH
- Mitochondrial Diseases * genetics MeSH
- Mutation genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Clinical Study MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20016478
- 003
- CZ-PrNML
- 005
- 20240522132446.0
- 007
- ta
- 008
- 201021s2016 xxk f 000 0|eng||
- 009
- AR
- 024 0_
- $a 10.1136/jmedgenet-2016-103910 $2 DOI
- 035 __
- $a (Pubmed)27412952
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxk
- 100 1_
- $a Ng, Yi Shiau $u Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
- 245 14
- $a The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease / $c Yi Shiau Ng, Charlotte L Alston, Daria Diodato, Andrew A Morris, Nicole Ulrick, Stanislav Kmoch, Josef Houštěk, Diego Martinelli, Alireza Haghighi, Mehnaz Atiq, Montserrat Anton Gamero, Elena Garcia-Martinez, Hana Kratochvílová, Saikat Santra, Ruth M Brown, Garry K Brown, Nicola Ragge , Ahmad Monavari, Karen Pysden, Kirstine Ravn, Jillian P Casey, Arif Khan, Anupam Chakrapani, Grace Vassallo, Cas Simons, Karl McKeever, Siobhan O'Sullivan, Anne-Marie Childs, Elsebet Østergaard, Adeline Vanderver, Amy Goldstein , Julie Vogt, Robert W Taylor, Robert McFarland
- 520 9_
- $a 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.
- 650 17
- $a mitochondriální nemoci $x genetika $7 D028361 $2 czmesh
- 650 _7
- $a mutace $x genetika $7 D009154 $2 czmesh
- 650 _7
- $a genetické asociační studie $7 D056726 $2 czmesh
- 650 _7
- $a lidé $7 D006801 $2 czmesh
- 650 _7
- $a dítě $7 D002648 $2 czmesh
- 653 00
- $a RMND1
- 655 _7
- $a práce podpořená grantem $7 D013485 $2 czmesh
- 655 _7
- $a klinická studie $7 D000068397 $2 czmesh
- 700 1_
- $a L Alston, Charlotte $u Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
- 700 1_
- $a Diodato, Daria
- 700 1_
- $a Morris, Andrew A
- 700 1_
- $a Ulrick, Nicole
- 700 1_
- $a Kmoch, Stanislav, $d 1963- $7 xx0056529 $u First Faculty of Medicine, Institute for Inherited Metabolic Disorders, Charles University in Prague, Prague, Czech Republic
- 700 1_
- $a Houštěk, Josef, $d 1947- $7 xx0030591 $u Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
- 700 1_
- $a Martinelli, Diego
- 700 1_
- $a Haghighi, Alireza
- 700 1_
- $a Atiq, Mehnaz
- 700 1_
- $a Gamero, Montserrat Anton
- 700 1_
- $a Garcia-Martinez, Elena
- 700 1_
- $a Kratochvílová, Hana $7 _AN065995 $u Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Santra, Saikat
- 700 1_
- $a Brown, Ruth M.
- 700 1_
- $a Brown, Garry K.
- 700 1_
- $a Ragge, Nicola
- 700 1_
- $a Monavari, Ahmad
- 700 1_
- $a Pysden, Karen
- 700 1_
- $a Ravn, Kirstine
- 700 1_
- $a Casey, Jillian P.
- 700 1_
- $a Khan, Arif
- 700 1_
- $a Chakrapani, Anupam
- 700 1_
- $a Vassallo, Grace
- 700 1_
- $a Simons, Cas
- 700 1_
- $a McKeever, Karl
- 700 1_
- $a O'Sullivan, Siobhan
- 700 1_
- $a Childs, Anne-Marie
- 700 1_
- $a Østergaard, Elsebet
- 700 1_
- $a Vanderver, Adeline
- 700 1_
- $a Goldstein, Amy
- 700 1_
- $a Vogt, Julie
- 700 1_
- $a Taylor, Robert W. $u Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
- 700 1_
- $a McFarland, Robert $u Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
- 773 0_
- $t Journal of medical genetics $x 0022-2593 $g Roč. 53, č. 11 (2016), s. 768-775 $w MED00002790
- 910 __
- $a ABA008 $y 0 $z 0
- 990 __
- $a 20201021104354 $b ABA008
- 991 __
- $a 20240522132441 $b ABA008
- 999 __
- $a kom $b bmc $g 1574734 $s 1106654
- BAS __
- $a 3
- BMC __
- $a 2016 $b 53 $c 11 $d 768-775 $x MED00002790 $i 0022-2593 $m Journal of medical genetics
- GRA __
- $a NV15-28208A $p MZ0
- LZP __
- $c NLK120 $d 20240522 $a 2020-grant
