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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00469548" target="_blank" >RIV/67985823:_____/16:00469548 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/16:10329593 RIV/00064165:_____/16:10329593

Výsledek na webu

<a href="http://dx.doi.org/10.1136/jmedgenet-2016-103910" target="_blank" >http://dx.doi.org/10.1136/jmedgenet-2016-103910</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jmedgenet-2016-103910" target="_blank" >10.1136/jmedgenet-2016-103910</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medical Genetics

ISSN

0022-2593

e-ISSN

—

Svazek periodika

53

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

768-775

Kód UT WoS článku

000387977600008

EID výsledku v databázi Scopus

2-s2.0-84978870767