Molecular genetics of hereditary sensory neuropathies

Neuromolecular Med. 2006;8(1-2):147-58. doi: 10.1385/nmm:8:1-2:147.

Abstract

Hereditary sensory neuropathies (HSN), also known as hereditary sensory and autonomic neuropathies (HSAN), are a clinically and genetically heterogeneous group of disorders. They are caused by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Both congenital and juvenile to adulthood onset is possible. Currently, the classification of the HSN depends on the mode of inheritance, age at onset, and clinical presentation. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Spontaneous fractures and neuropathic arthropathy are frequent complications and often necessitate amputations. Autonomic features vary between different subgroups. Distal muscle weakness and wasting may be present and is sometimes so prominent that it becomes difficult to distinguish HSN from Charcot-Marie-Tooth syndrome. Recent major advances in molecular genetics have led to the identification of seven gene loci and six-disease causing genes for autosomal-dominant and autosomal-recessive HSN. These genes have been shown to play roles in lipid metabolism and the regulation of intracellular vesicular transport, but also a presumptive transcriptional regulator, a nerve growth factor receptor, and a nerve growth factor have been described among the causative genes in HSN. Nevertheless, it remains unclear how mutations in the known genes lead to the phenotype of HSN. In this review, we summarize the recent progress of the molecular genetics of the HSN and the implicated genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chaperonin Containing TCP-1
  • Chaperonins / genetics
  • Chaperonins / metabolism
  • Chromosome Disorders
  • Genes, Dominant
  • Genes, Recessive
  • Genotype
  • Hereditary Sensory and Motor Neuropathy / genetics*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Hereditary Sensory and Motor Neuropathy / physiopathology
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Minor Histocompatibility Antigens
  • Molecular Biology
  • Mutation
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phenotype
  • Protein-Serine-Threonine Kinases
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism
  • Serine C-Palmitoyltransferase
  • Transcriptional Elongation Factors
  • WNK Lysine-Deficient Protein Kinase 1
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Carrier Proteins
  • Elp1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Minor Histocompatibility Antigens
  • NGF protein, human
  • Nerve Tissue Proteins
  • Transcriptional Elongation Factors
  • rab7 protein
  • Nerve Growth Factor
  • Acyltransferases
  • SPTLC1 protein, human
  • Serine C-Palmitoyltransferase
  • Receptor, trkA
  • Protein-Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human
  • Chaperonin Containing TCP-1
  • Chaperonins
  • rab GTP-Binding Proteins