Ndufs4 related Leigh syndrome: A case report and review of the literature

被引：48

作者：

Dario Ortigoza-Escobar, Juan ^{[1
,10
]}

Oyarzabal, Alfonso ^{[2
]}

Montero, Raquel ^{[3
]}

Artuch, Rafael ^{[3
,9
]}

Jou, Cristina ^{[4
,9
]}

Jimenez, Cecilia ^{[4
,9
]}

Gort, Laura ^{[5
,9
]}

Briones, Paz ^{[5
,8
,9
]}

Muchart, Jordi ^{[6
]}

Lopez-Gallardo, Ester ^{[7
,9
]}

Emperador, Sonia ^{[7
,9
]}

Ruiz Pesini, Eduardo ^{[7
,9
]}

Montoya, Julio ^{[7
,9
]}

Perez, Belen ^{[2
]}

Rodriguez-Pombo, Pilar ^{[2
]}

Perez-Duenas, Belen ^{[1
,9
]}

机构：

[1] Univ Barcelona, St Joan Deu Hosp, Div Child Neurol, E-08007 Barcelona, Spain

[2] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa CSIC UAM, Ctr Diagnost Enfermedades Mol CEDEM, Dept Biol Mol,IDIPAZ, E-28049 Madrid, Spain

[3] Univ Barcelona, St Joan de Deu Hosp, Div Biochem, E-08007 Barcelona, Spain

[4] Univ Barcelona, St Joan de Deu Hosp, Pathol, E-08007 Barcelona, Spain

[5] Hosp Clin Barcelona, Dept Biochem & Mol Genet, Div Inborn Errors Metab IBC, Barcelona, Spain

[6] Univ Barcelona, St Joan de Deu Hosp, Radiol, E-08007 Barcelona, Spain

[7] Univ Zaragoza, ISCIII, E-50009 Zaragoza, Spain

[8] ISCIII, CSIC, Barcelona, Spain

[9] ISCIII, Ctr Biomed Res Rare Dis CIBERER, Barcelona, Spain

[10] Fdn Hosp Asilo Granollers, Div Child Neurol, Barcelona, Spain

来源：

MITOCHONDRION | 2016年 / 28卷

关键词：

Leigh syndrome; Respiratory chain complex I; NDUFS4; BN-PAGE; Next generation sequencing; COMPLEX-I DEFICIENCY; THIAMINE TRANSPORTER-2 DEFICIENCY; ALLOWS RAPID IDENTIFICATION; RESPIRATORY-CHAIN; AQDQ SUBUNIT; MITOCHONDRIAL DISEASE; NONSENSE MUTATION; GENE; DEHYDROGENASE; NFU1;

D O I：

10.1016/j.mito.2016.04.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

引用

页码：73 / 78

页数：6

共 50 条

[1] Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention
van de Wal, Melissa A. E.
Adjobo-Hermans, Merel J. W.
Keijer, Jaap
Schirris, Tom J. J.
Homberg, Judith R.
Wieckowski, Mariusz R.
Grefte, Sander
van Schothorst, Evert M.
van Karnebeek, Clara
Quintana, Albert
Koopman, Werner J. H.
BRAIN, 2022, 145 (01) : 45 - 63
[2] NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement
Leshinsky-Silver, E.
Lebre, Anne-Sophie
Minai, Limor
Saada, Ann
Steffann, Julie
Cohen, Sarit
Roetig, Agnes
Munnich, Arnold
Lev, Dorit
Lerman-Sagie, Tally
MOLECULAR GENETICS AND METABOLISM, 2009, 97 (03) : 185 - 189
[3] NDUFS6 related Leigh syndrome: a case report and review of the literature
Rouzier, Cecile
Chaussenot, Annabelle
Fragaki, Konstantina
Serre, Valerie
Ait-El-Mkadem, Samira
Richelme, Christian
Paquis-Flucklinger, Veronique
Bannwarth, Sylvie
JOURNAL OF HUMAN GENETICS, 2019, 64 (07) : 637 - 645
[4] A Novel NDUFS4 Frameshift Mutation Causes Leigh Disease in the Hutterite population
Lamont, Ryan E.
Beaulieu, Chandree L.
Bernier, Francois P.
Sparkes, Rebecca
Innes, A. Micheil
Jackel-Cram, Candice
Ober, Carole
Parboosingh, Jillian S.
Lemire, Edmond G.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2017, 173 (03) : 596 - 600
[5] Peripheral macrophages drive CNS disease in the Ndufs4(-/-) model of Leigh syndrome
Hanaford, Allison R.
Khanna, Asheema
Truong, Vivian
James, Katerina
Chen, Yihan
Mulholland, Michael
Kayser, Bernhard
Liao, Ryan W.
Sedensky, Margaret
Morgan, Phil
Baerchst, Nathan
Kalia, Vandana
Sarkar, Surojit
Johnson, Simon C.
BRAIN PATHOLOGY, 2023, 33 (06)
[6] Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome
Stokes, Julia C.
Bornstein, Rebecca L.
James, Katerina
Park, Kyung Yeon
Spencer, Kira A.
Vo, Katie
Snell, John C.
Johnson, Brittany M.
Morgan, Philip G.
Sedensky, Margaret M.
Baertsch, Nathan A.
Johnson, Simon C.
JCI INSIGHT, 2022, 7 (05)
[7] A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome
Assouline, Z.
Jambou, M.
Rio, M.
Bole-Feysot, C.
de Lonlay, P.
Barnerias, C.
Desguerre, I.
Bonnemains, C.
Guillermet, C.
Steffann, J.
Munnich, A.
Bonnefont, J. P.
Roetig, A.
Lebre, A. S.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2012, 1822 (06): : 1062 - 1069
[8] Microglial response promotes neurodegeneration in the Ndufs4 KO mouse model of Leigh syndrome
Aguilar, Kevin
Comes, Gemma
Canal, Carla
Quintana, Albert
Sanz, Elisenda
Hidalgo, Juan
GLIA, 2022, 70 (11) : 2032 - 2044
[9] NDUFS4-related Leigh syndrome in Hutterites
Finsterer, Josef
Zarrouk-Mahjoub, Sinda
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2017, 173 (05) : 1450 - 1451
[10] Early-age Ndufs4 knockout mice are an inappropriate animal model of Leigh syndrome
Josef Finsterer
Radiological Physics and Technology, 2019, 12 : 230 - 231

← 1 2 3 4 5 →