Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings
: 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
: London
: 2025
: Mitochondrion
: MITOCHONDRION
: MITOCHONDRION
: 102007
: 81
: 9
: 1567-7249
: 1872-8278
DOI: https://doi.org/10.1016/j.mito.2025.102007
: https://doi.org/10.1016/j.mito.2025.102007
: https://research.utu.fi/converis/portal/detail/Publication/485204647
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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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.
