Skip to main content

Advertisement

SpringerLink
Log in

Additive effect of DNAJC30 and NDUFA9 mutations causing Leigh syndrome

  • Letter to the Editors
  • Published:
Journal of Neurology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Data availability

The authors confirm that the data supporting the findings of this study are available upon reasonable request.

References

  1. Tebbenkamp ATN, Varela L, Choi J, Paredes MI, Giani AM, Song JE, Sestan-Pesa M, Franjic D, Sousa AMM, Liu ZW, Li M, Bichsel C, Koch M, Szigeti-Buck K, Liu F, Li Z, Kawasawa YI, Paspalas CD, Mineur YS, Prontera P, Merla G, Picciotto MR, Arnsten AFT, Horvath TL, Sestan N (2018) The 7q11.23 protein DNAJC30 interacts with ATP synthase and links mitochondria to brain development. Cell 175:1088-1104.e23. https://doi.org/10.1016/j.cell.2018.09.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Stenton SL, Sheremet NL, Catarino CB, Andreeva NA, Assouline Z, Barboni P, Barel O, Berutti R, Bychkov I, Caporali L, Capristo M, Carbonelli M, Cascavilla ML, Charbel Issa P, Freisinger P, Gerber S, Ghezzi D, Graf E, Heidler J, Hempel M, Heon E, Itkis YS, Javasky E, Kaplan J, Kopajtich R, Kornblum C, Kovacs-Nagy R, Krylova TD, Kunz WS, La Morgia C, Lamperti C, Ludwig C, Malacarne PF, Maresca A, Mayr JA, Meisterknecht J, Nevinitsyna TA, Palombo F, Pode-Shakked B, Shmelkova MS, Strom TM, Tagliavini F, Tzadok M, van der Ven AT, Vignal-Clermont C, Wagner M, Zakharova EY, Zhorzholadze NV, Rozet JM, Carelli V, Tsygankova PG, Klopstock T, Wittig I, Prokisch H (2021) Impaired complex I repair causes recessive Leber’s hereditary optic neuropathy. J Clin Invest 131:e138267. https://doi.org/10.1172/JCI138267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zawadzka M, Krygier M, Pawłowicz M, Wilke MVMB, Rutkowska K, Gueguen N, Desquiret-Dumas V, Klee EW, Schimmenti LA, Sławek J, Procaccio V, Płoski R, Mazurkiewicz-Bełdzińska M (2022) Expanding the phenotype of DNAJC30-associated Leigh syndrome. Clin Genet 102(5):438–443. https://doi.org/10.1111/cge.14196. (Epub 2022 Jul 29. PMID: 35861300)

    Article  CAS  PubMed  Google Scholar 

  4. Wiggs JL (2021) DNAJC30 biallelic mutations extend mitochondrial complex I-deficient phenotypes to include recessive Leber’s hereditary optic neuropathy. J Clin Invest 131(6):e147734. https://doi.org/10.1172/JCI147734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kieninger S, Xiao T, Weisschuh N, Kohl S, Rüther K, Kroisel PM, Brockmann T, Knappe S, Kellner U, Lagrèze W, Mazzola P, Haack TB, Wissinger B, Tonagel F (2022) DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber’s hereditary optic neuropathy and optic atrophy. J Med Genet 59:1027–1034. https://doi.org/10.1136/jmedgenet-2021-108235

    Article  CAS  PubMed  Google Scholar 

  6. Schubert Baldo M, Vilarinho L (2020) Molecular basis of Leigh syndrome: a current look. Orphanet J Rare Dis 15(1):31. https://doi.org/10.1186/s13023-020-1297-9

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tolomeo D, Orsucci D, Nesti C, Baldacci J, Battini R, Bruno C, Bruno G, Cassandrini D, Doccini S, Donati MA, Ferrari A, Fiori S, Fiorillo C, Guerrini R, Mari F, Montomoli M, Pochiero F, Procopio E, Ruggiero L, Sampaolo S, Sicca F, Ticci C, Rubegni A, Santorelli FM (2021) The Diagnostic Approach to Mitochondrial Disorders in Children in the Era of Next-Generation Sequencing: A 4-Year Cohort Study. J Clin Med 10:3222. https://doi.org/10.3390/jcm10153222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. van den Bosch BJ, Gerards M, Sluiter W, Stegmann AP, Jongen EL, Hellebrekers DM, Oegema R, Lambrichs EH, Prokisch H, Danhauser K, Schoonderwoerd K, de Coo IF, Smeets HJ (2021) Defective NDUFA9 as a novel cause of neonatally fatal complex I disease. J Med Genet 49:10–15. https://doi.org/10.1136/jmedgenet-2011-100466

    Article  Google Scholar 

  9. Vetro A, Nielsen HN, Holm R, Hevner RF, Parrini E, Powis Z, Møller RS, Bellan C, Simonati A, Lesca G, Helbig KL, Palmer EE, Mei D, Ballardini E, Van Haeringen A, Syrbe S, Leuzzi V, Cioni G, Curry CJ, Costain G, Santucci M, Chong K, Mancini GMS, Clayton-Smith J, Bigoni S, Scheffer IE, Dobyns WB, Vilsen B, Guerrini R (2021) ATP1A2/A3-collaborators. ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain 144:1435–1450. https://doi.org/10.1093/brain/awab052

    Article  PubMed  Google Scholar 

  10. Sgarbi G, Matarrese P, Pinti M, Lanzarini C, Ascione B, Gibellini L, Dika E, Patrizi A, Tommasino C, Capri M, Cossarizza A, Baracca A, Lenaz G, Solaini G, Franceschi C, Malorni W, Salvioli S (2014) Mitochondria hyperfusion and elevated autophagic activity are key mechanisms for cellular bioenergetic preservation in centenarians. Aging (Albany NY) 6:296–310. https://doi.org/10.18632/aging.100654

    Article  PubMed  Google Scholar 

  11. Stenton SL, Tesarova M, Sheremet NL, Catarino C, Carelli V, Ciara E, Curry K, Engvall M, Fleming LR, Freisinger P, Iwanicka-Pronicka K, Jurkiewicz E, Klopstock T, Koenig MK, Kolářová H, Kousal B, Krylova T, La Morgia C, Nosková L, Piekutowska-Abramczuk D, Russo SN, Stránecký V, Tóthová I, Träisk F, Prokisch H (2022) DNAJC30 defect: a frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome. Brain 145(5):1624–1631. https://doi.org/10.1093/brain/awac052

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ardissone A, Bruno C, Diodato D, Donati A, Ghezzi D, Lamantea E, Lamperti C, Mancuso M, Martinelli D, Primiano G, Procopio E, Rubegni A, Santorelli F, Schiaffino MC, Servidei S, Tubili F, Bertini E, Moroni I (2021) Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases. Orphanet J Rare Dis 16:413. https://doi.org/10.1186/s13023-021-02029-3

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was partially supported by grants from the Italian Ministry of Health Ricerca Corrente (to C.N., A.R. and F.M.S.), Rete IDEA and Rete RIN (to F.M.S.), MITO-NEXT (to F.M.S.), MiRe2020 (to F.M.S.). R.G. is supported by the Tuscany Region Call for Health 2018 (grant DECODE-EE) and the Brain project by Fondazione CA.RI.FI.; R.G. and A.V. are members of the European Reference Networks (ERNs) EpiCARE and ITHACA.

Author information

Author notes

  1. Claudia Nesti, Chiara Ticci have contributed equally.

Authors and Affiliations

  1. Molecular Medicine for Neurodegenerative and Neuromuscular Disease Unit, IRCCS Stella Maris Foundation, Via Dei Giacinti 2, 56128, Pisa, Italy

    Claudia Nesti, Anna Rubegni, Stefano Doccini & Filippo M. Santorelli

  2. Neuroscience Department, IRCCS Meyer Children’s Hospital, Florence, Italy

    Chiara Ticci, Giusi Scaturro, Annalisa Vetro, Renzo Guerrini & Elena Procopio

Authors
  1. Claudia Nesti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Ticci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Rubegni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefano Doccini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giusi Scaturro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Annalisa Vetro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renzo Guerrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Filippo M. Santorelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Elena Procopio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Claudia Nesti or Anna Rubegni.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards statement

This study was approved by the Tuscany Regional Pediatric Ethics Committee. All the procedures complied with the Helsinki Declaration of 1975. Genetic studies, muscle and skin punch biopsies were performed with parental written informed consent.

Supplementary Information

Below is the link to the electronic supplementary material.

415_2023_11673_MOESM1_ESM.tif

Supplementary figure S1: Mitochondrial organization in cultured skin fibroblasts from DNAJC30 patient (Pt) and Control. The mitochondrial morphology was observed by fluorescence microscopy using the MitoTracker™ Red CMXRos dye (Thermo Fisher; M7512) and skeletonized images were generated post-acquisition, suggesting a hyperfused network in the patient. Images were acquired using a Nikon Ti2-E inverted microscope equipped with ViCo structured light system, using a ×60 Plan Apocr λ (NA = 1.40) oil immersion objective and an TRITC filter set. Scale bar: 10 µm

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nesti, C., Ticci, C., Rubegni, A. et al. Additive effect of DNAJC30 and NDUFA9 mutations causing Leigh syndrome. J Neurol 270, 3266–3269 (2023). https://doi.org/10.1007/s00415-023-11673-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-023-11673-7

Search

Navigation