To identify genetic causes of neurological diseases, we utilize genome-wide next-generation sequencing approaches. We investigate the molecular mechanisms of disease mutations by generating patient-specific motor neurons from reprogrammed skin fibroblasts.

• Threshold of heteroplasmic truncating MT-ATP6 mutation in reprogramming, Notch hyperactivation and motor neuron metabolism
• ITPR3 encoding IP3 receptor type 3 (IP3R3) is a disease gene for dominant Charcot-Marie-Tooth disease
• Mitochondrial intermembrane space proteins CHCHD2 or CHCHD10 impact respiration in human motor neurons
• Distinct effects on mRNA export factor GANP cause neuropathy plus phenotypes
• Absence of neurofilament light causes early-onset neuropathy
• ATAD3A in dominant hereditary spastic paraplegia
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We investigate the consequences of disturbed mitochondrial proteostasis on cell and tissue function, as well as the role of mitochondria in maintaining cellular proteostasis. In relation to human disease, we are particularly interested in mitochondrial aminoacyl-tRNA synthetases that are associated with multiple tissue-specific mitochondrial diseases.

• Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure (preprint)
• Redox regulation of GRPEL2, the co-chaperone of mitochondrial HSP70
• Editing activity by mitochondrial alanyl-tRNA synthetase is essential in mammals

This project aims to evaluate the effectiveness and impact of current personalised genomic technology as the first-line diagnostic tool in progressive neurological diseases of adults and children. This is a collaboration between University of Helsinki, Helsinki University Hospital, and VATT Institute for Economic Research.

• PYROXD1 underlies adult-onset Limb-Girdle-type muscular dystrophy
• Effectiveness of clinical exome sequencing in adult patients with difficult-to-diagnose neurological disorders