Genetics in hereditary neuropathies

Hereditary neuropathies, also known as Charcot-Marie-Tooth (CMT) syndrome, are the most common inherited disorders of the peripheral nervous system with an estimated prevalence of 1 in 2500. However, these disorders are obviously underdiagnosed in Austria. Age at onset is usually during the first or second decade of life or sometimes later. Hallmark features are slowly progressive gait abnormalities and weakness in the hands due to mild to prominent muscle wasting in the distal parts of the upper and lower limbs. Distal sensory loss may also be present. Molecular genetic examinations in the past 20 years have shown marked genetic heterogeneity with the identification of mutations in multiple different genes. Very recently, reports have shown that ascorbic acid and progesterone antagonists can successfully treat rodent models of the most common form of CMT, i.e. CMT 1a syndrome. In many cases it is difficult to distinguish between inherited and acquired forms of neuropathies. In this research project we aim to recruit CMT patients and CMT families in all parts of Austria. We will perform detailed clinical, electrophysiological and genetic examinations and will establish a CMT database. Based on these results phenotype-genotype and epidemiological studies will be carried out. Our studies will help to make this common but still only little known inherited disorders of the peripheral nervous system public in Austria to achieve international standards. Patients with neuropathies will benefit by improved diagnosis, adequate treatment and genetic counselling. Finally, patients with CMT syndrome will once be available and characterised for clinical trials. Further, we aim to identify new CMT loci and disease causing genes and intend to perform functional studies. Phenotype-genotype correlation studies will enable setting up guidelines for effective and successful testing of CMT patients. Finally, these studies will lead to a better understanding of the pathogenesis of the hereditary neuropathies and enables to develop therapies.

Hereditary neuropathies, also known as Charcot-Marie-Tooth (CMT) syndrome, are the most common inherited disorders of the peripheral nervous system with an estimated prevalence of 1 in 2500. However, these disorders are obviously underdiagnosed in Austria. Age at onset is usually during the first or second decade of life or sometimes later. Hallmark features are slowly progressive gait abnormalities and weakness in the hands due to mild to prominent muscle wasting in the distal parts of the upper and lower limbs. Distal sensory loss may also be present. Molecular genetic examinations in the past 20 years have shown marked genetic heterogeneity with the identification of mutations in multiple different genes. Very recently, reports have shown that ascorbic acid and progesterone antagonists can successfully treat rodent models of the most common form of CMT, i.e. CMT 1a syndrome. In many cases it is difficult to distinguish between inherited and acquired forms of neuropathies. In this research project we aim to recruit CMT patients and CMT families in all parts of Austria. We will perform detailed clinical, electrophysiological and genetic examinations and will establish a CMT database. Based on these results phenotype-genotype and epidemiological studies will be carried out. Our studies will help to make this common but still only little known inherited disorders of the peripheral nervous system public in Austria to achieve international standards. Patients with neuropathies will benefit by improved diagnosis, adequate treatment and genetic counselling. Finally, patients with CMT syndrome will once be available and characterised for clinical trials. Further, we aim to identify new CMT loci and disease causing genes and intend to perform functional studies. Phenotype-genotype correlation studies will enable setting up guidelines for effective and successful testing of CMT patients. Finally, these studies will lead to a better understanding of the pathogenesis of the hereditary neuropathies and enables to develop therapies.