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Project

Tackling the missing heritability of inherited peripheral neuropathies: towards improved patient care, better mechanistic insights and identification of determinants driving phenotypic diversity.

Inherited Peripheral Neuropathies (IPN) constitute a large and diverse group of disorders causing length-dependent neurodegeneration of axons in the peripheral nervous system (PNS). As many other neuromuscular disorders, IPN are chronic, debilitating and in some instances life-threatening conditions resulting in tremendous disease burden for patients and society. Affecting 1 in 2500 individuals, IPN share the challenges common to other 'rare disorders' namely substantial delays in diagnosis due to lack of reliable diagnostic tools; lack of specialized centres and standards for optimal patient care; lack of fundamental understanding of the mechanisms of disease and the absence of effective therapies. For three types of IPN (pure motor forms, pure sensory forms and congenital forms) the 'missing heritability' is as high as 70%. In this project we will start from biobanking of patients with the above-mentioned understudied types of IPN and we will systematically map out the phenotypic characteristics. In parallel, we will conduct large-scale genetic studies using next-generation sequencing techniques in these cohorts. By doing so we will tackle the existing knowledge gap in the genetic groundwork of PNS disease. This will evidently improve patient diagnosis but will at the same time significantly enlarge our understanding of the crucial mechanisms leading to axonal degeneration of the peripheral nervous system. Thirdly we aim to study the striking variability in disease severity of IPN through detailed genotype-phenotype correlation. Ultimately this will facilitate future studies designing reliable 'disease biomarkers' amenable for disease severity assessment on the one hand and the identification of novel targets for future therapeutic strategies on the other hand.
Date:1 Oct 2016 →  30 Sep 2020
Keywords:NATURAL HISTORY, NEUROGENETICS, NEUROMUSCULAR DISEASES, NEURODEGENERATION
Disciplines:Genetics, Systems biology, Molecular and cell biology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing