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, Päivi; Suo-Palosaari, Maria; Uusimaa, Johanna (2025-01-31)
Elsevier
31.01.2025
Jaakko Oikarainen, Reetta Hinttala, Naemeh Nayebzadeh, Salla M. Kangas, Katariina Mankinen, Elisa Rahikkala, Hannaleena Kokkonen, Päivi Vieira, Maria Suo-Palosaari, Johanna Uusimaa, Novel intronic variant in NDUFS7 gene results in mitochondrial complex I assembly defect with early basal ganglia and midbrain involvement with progressive neuroimaging findings, Mitochondrion, Volume 81, 2025, 102007, https://doi.org/10.1016/j.mito.2025.102007.
https://creativecommons.org/licenses/by/4.0/
© 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202502131622
https://urn.fi/URN:NBN:fi:oulu-202502131622
Tiivistelmä
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.
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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