Molecular genetics of peripheral neuropathies

Molecular genetic techniques have identified the mutational basis of many inherited neuropathies due to metabolic disorders, including porphyrias, leukodystrophies and other storage diseases. Inherited amyloid neuropathies may be caused by mutations in three different genes: those for gelsolin, apolipoprotein A1 and, most frequently, transthyretin. The classification of hereditary motor and sensory neuropathies has been changed by the identification of underlying mutations encoding myelin proteins, P0 and peripheral myelin protein 22 and connexin 32. Peripheral myelin protein 22 gene defects are also seen in hereditary liability to pressure palsies. There is peripheral sensory nerve involvement in one of the diseases caused by an unstable trinucleotide repeat sequence: X-linked bulbospinal neuronopathy. These advances can be translated into clinical practice, leading to improved diagnosis and genetic counselling.