A study lead by Uusimaa and Hinttala reveals a new gene required for normal fetal development and severe childhood multiorgan disease

Professor of Pediatric Neurology, Johanna Uusimaa, and Academy Research Fellow, Docent Reetta Hinttala together with their research team and collaborators have described a new, fatal multiorgan disease in Finnish pediatric patients. The disease was named FINCA (Fibrosis, Neurodegeneration and Cerebral Angiomatosis). Patients had previously undescribed formation of connective tissue in the lungs, neurodegeneration and increased vasculature formation in the brain. As a result of their study, mutations were found for the first time in the NHLRC2 gene from the FINCA patients. Using genetically modified mouse and zebra fish models, NHLRC2 protein with previously unknown function was found to be vital for normal fetal development and maintenance of multi-organ homeostasis.

The patients in Northern-Finland have globally unique genetic background, which enables the identification of novel recessive diseases and their causative mutations  in the genes with previously unknown functions. The study was carried out at the Oulu University Hospital and in the Division of Pediatric Neurology of the PEDEGO Research Unit at the University of Oulu. Most of the researchers involved in the study work at the Oulu University Hospital and at the Biocenter Oulu and the Medical Research Center Oulu. In addition, researchers from the Universities of Tampere and Helsinki, the McGill University of Canada and the Johns Hopkins University in the USA participated in the research. The main funding sources of the study were the University of Oulu, the Oulu University Hospital, the Academy of Finland, the Research Foundation for Pediatric Disorders, the Sigrid Juselius Foundation and the Alma and KA Snellman Foundation.

The results of the study were published in the journal Acta Neuropatologica published by Springer Nature, one of the most prestigious journals in the field of neurological sciences.

NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA): characterisation of a novel cerebropulmonary disease

Uusimaa J, Kaarteenaho R, Paakkola T, Tuominen H, Karjalainen MK, Nadaf J, Varilo T, Uusi-Mäkelä M, Suo-Palosaari M, Pietilä I, Hiltunen AE, Ruddock L, Alanen H, Biterova E, Miinalainen I, Salminen A, Soininen R, Manninen A, Sormunen R, Kaakinen M, Vuolteenaho R, Herva R, Vieira P, Dunder T, Kokkonen H, Moilanen JS, Rantala H, Nogee LM, Majewski J, Rämet M, Hallman M, Hinttala R.

Acta Neuropathol. 2018 Feb 8. doi: 10.1007/s00401-018-1817-z. [Epub ahead of print]

Last updated: 16.2.2018