Clinical Genetics

Mitochondrial Genetics

This research line focuses on the characterization of:

  1. Abnormalities in mitochondrial genes, gene expression and gene function in inherited and complex diseases, like neuromuscular disorders, neurological syndromes and cardiomyopathies, in human patients and animal models, but alos in therapy-predictions (radiotherapy).
  2. Interventions that can modulate mitochondrial activity and promote health and prevent or ameliorate disease manifestations.
  3. Preventing the transmission of OXPHOS disease due to mutations in the mitochondrial DNA by Preimplantation Genetic Diagnosis (PGD).

The research programme that goes from bench to bedside and back is highly technology and bioinformatics driven. It covers fundamental, translational and applied research alike. Research is conducted in close connection to and supported by disease- and patient-oriented funds, like Metakids and Ride4Kids. All research is embedded in the diagnostic work of the unit Clinical Genomics (department Clinical Genetics, Maastricht UMC+), generating a close connection to patients and patient demands.

The research team has a broad and longstanding network in the field of mitochondrial disease. The applicant was co-ordinator of the EU-FP-STREP 'Mitochondrial diseases: From Bedside to Genome to Bedside' (V. Tiranti, PhD/Prof. M. Zeviani, PhD, Milano; prof. P.F. Chinnery, PhD/Prof. D. Turnbull, PhD, Newcastle; L. van den Heuvel, PhD/Prof. J. Smeitink, PhD, Nijmegen; prof. A. Munnich, PhD, Paris).

New sequencing approaches are being developed with the Technische Universität Münich (H. Prokisch, PhD) and stem cell therapy with the Sampaolesi, PhD (Interdepartmental stem cell institute of the KU Leuven, Belgium).

Publications

Gerards et al. (2013) Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome. Brain. 136(Pt 3):882-90.

Sallevelt SC, et al. (2013) Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success. J Med Genet. 50(2):125-32.

Hellebrekers DM, et al. (2012) PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring. Hum Reprod Update 18(4):341-9.

van den Bosch BJ, et al. (2012) Defective NDUFA9 as a novel cause of neonatally fatal complex I disease. J Med Genet. 49(1):10-5.

van Tienen FH, et al. (2012) Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes. J Clin Endocrinol Metab. 97(9):3261-9.

Voets AM, et al. (2012) Transcriptional changes in OXPHOS complex I deficiency are related to anti-oxidant pathways and could explain the disturbed calcium homeostasis. Biochim Biophys Acta 1822(7):1161-8.

Gerards M, et al. (2011) Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene. Brain 134(Pt 1):210-9.

Team leaders

Prof. Bert Smeets, Florence van Tienen, PhD, Radek Szklarczyk, PhD
E: bert.smeets@maastrichtuniversity.nl

School

GROW