Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings - UTU Research Portal

A1 Refereed original research article in a scientific journal

Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings

Authors: Oikarainen, Jaakko; Hinttala, Reetta; Nayebzadeh, Naemeh; Kangas, Salla M.; Mankinen, Katariina; Rahikkala, Elisa; Kokkonen, Hannaleena; Vieira, Paivi; Suo-Palosaari, Maria; Uusimaa, Johanna

Publisher: ELSEVIER SCI LTD

Publishing place: London

Publication year: 2025

Journal: Mitochondrion

Journal name in source: MITOCHONDRION

Journal acronym: MITOCHONDRION

Article number: 102007

Volume: 81

Number of pages: 9

ISSN: 1567-7249

eISSN: 1872-8278

DOI: https://doi.org/10.1016/j.mito.2025.102007

Web address : https://doi.org/10.1016/j.mito.2025.102007

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/485204647

Abstract

Leigh syndrome is the most common phenotype of mitochondrial disorders in children. This study demonstrates clinical, neuroradiological, and molecular genetic findings in siblings with Leigh syndrome and isolated complex I assembly defect associated with intronic c.16 + 5G > A variant in the NDUFS7 gene. Whole exome sequencing was carried out to identify the causative variant. The gene and protein expression of NDUFS7 were studied using patient-derived fibroblasts. Assembly of mitochondrial respiratory chain enzymes was analyzed using Blue Native PAGE. This study shows that the NDUFS7 c.16 + 5G > A variant (rs375282422) has a causative role in Leigh syndrome. Evolution of neuroimaging findings related to this gene variant are demonstrated.

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Funding information in the publication:
This work was supported by the Arvo and Lea Ylppö Foundation, Stiftelsen Alma och K.A.
Snellman Säätiö, Oulun Lääketieteellinen Tutkimussäätiö (Oulu Medical Research Foundation), Academy of Finland (JU, decision 331436; RH, decisions no. 311934, 266498, 273790, 303996), Finnish Medical Foundation, Paediatric Research Foundation (RH, JU), and Competitive State Funding for Health Research (JU and MS-P), Oulu University
Hospital, Finland.