Public Defence: Anide Johansen
MSc Anide Johansen at Institute of Clinical Medicine will be defending the thesis “Biallelic Variants in MBOAT7 and TRAPPC6B as Novel Genetic Causes for Intellectual Disability with Epilepsy, Microcephaly and Autistic Features” for the degree of PhD (Philosophiae Doctor).
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Johannes Lemke, Institute of Human Genetics, Leipzig University Hospital, Germany
- Second opponent: Senior Scientist Nathalie Jurisch-Yaksi, Norwegian University of Science and Technology (NTNU)
- Third member and chair of the evaluation committee: Professor Magnar Bjørås, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor II Mathias Toft, Faculty of Medicine, University of Oslo
Professor Dag Erik Undlien, Faculty of Medicine, University of Oslo
Group Leader Kaja Kristine Selmer, Oslo University Hospital
In areas of the world where consanguineous marriages and inbreeding is more common, the occurrence of inherited diseases is high. These areas include parts of the Middle East, Central South Asia and South America. Intellectual disability is a genetic condition, often occurring in combination with other neurological presentations like epilepsy, autism and microcephaly. In this thesis we present multiple consanguineous families from the Middle East and South Central Asia, each with multiple children affected by familial autism, epilepsy and intellectual disability or microcephaly. Whole exome sequencing of affected subjects identified several biallelic, deleterious variants in two novel genes; MBOAT7 and TRAPPC6B that segregated with the disease. TRAPPC6B mutations were found in 6 patients diagnosed with microcephaly from birth, intellectual disability and autistic features. A zebrafish model of trappc6b knockdown showed decreased head along with abnormal neuronal activity and an increase in spontaneous neuronal firing. MBOAT7 was found to be mutated in six consanguineous families from the Middle East, where all affected children (16) presented with intellectual disability, epilepsy and autistic features. When knocking out mboat7 in specific cell types of the brain in mice, neuronal lineages created a cortical phenotype resembling the straight mboat7 knockout. Mboat7 knockout leads to cortical cell death around embryonic day 14.5, and subsequently thinner cortex and loss of neurons at E18.5. Knockout of cytosolic phospholipase A2 in the mboat7 knockout showed a rescue in cortical thickness by E18.5, suggesting a potential for treatment of human MBOAT7 disease.
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