Advances in the Generics of Hereditary Peripheral Neuripathies


    loading  Checking for direct PDF access through Ovid

Abstract

Recent advances in the molecular genetics of hereditary peripheral neuropathies have led to changes in the classification of these neuropathies. The hereditary motor and sensory neuropathies (HMSNs) include Charcot-Marie-Tooth disease, both the hypertrophic and neuronal forms of disease among others. The hypertrophic from (HMSN, type 1) is characterized by the presence of abundant omon bulbs pathologically and is caused by mutations in at least four separate genetic loci. The neuronal from (HMSN 2) is characterized by axonal loss on nerve biopsy and is caused by entirely separate genetic loci. The infantile hypertrophic hereditary neuropathy (Déjérine-Sottas disease, HMSN 3), which is characterized by abundant onion bulbs similar to HMSN 1, includes patients with mutations of either PMP-22 or MPZ. Among other hereditary motor and sensory neuropathies, the molecular basis of one form of infantile neuroaxonal dystrophy (Schindler disease) has been identified as absence of α-N-acetyl-D-galactosminidase activity, and the hereditary neuropathy with liability to develop pressure palsies and segmental thickening of myelin layers (tomaculous neuropathy) in volves a deletion of the PMP-2 locus on chromosome 17,. Among the hereditary sensory and autonomic neuropathies (HSANs), only the chromosomal region for the autosomal recessive familial dysautonomia (Riley-Day syndrome, HSAN 3) has been localized (Chromosome 9131-q33). Finally, the gene involved in the Portuguese, Swedish, Jewish, Maryland, Appalachian, German, and Indiana types of familial amyloid neuropathy has been identified as transtbyretin, with many of these separately identified kindreds showing the same mutation and others showing mutations with neuropathy result from mutations in the gelsolin gene and apolipoprotein A-I. The remarkable remarkable recent progress has clarified the molecular basis for the genetic heterogeneity of the clinical syndromes of hereditary peripheral neropathies and clarifies the relationships between genotype and clinical and pathologic phenotype.

    loading  Loading Related Articles