Disease relevance of Hereditary Sensory and Autonomic Neuropathies

• Human TRKA (NTRK1) encodes the receptor tyrosine kinases (RTKs) for nerve growth factor (NGF) and is the gene responsible for congenital insensitivity to pain with anhidrosis (CIPA), an autosomal recessive disorder characterized by a lack of pain sensation and anhidrosis [1].
• The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor [2].
• The map position of FKHL15 on 9q22 places the gene within the candidate regions for the cancer predisposition syndrome multiple self-healing squamous epitheliomata and the degenerative neurological disorder hereditary sensory neuropathy type I. This is a region frequently lost in squamous cell cancer [3].
• A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci [4].
• Capillary gas-liquid chromatography was used to analyze the fatty acid composition of normal heel fat pads from subjects without systemic disease (N = 8) and atrophied heels from patients with diabetic peripheral neuropathy (N = 4), rheumatoid arthritis (N = 1), peripheral vascular disease (N = 1), and hereditary sensory neuropathy (N = 1) [5].

Psychiatry related information on Hereditary Sensory and Autonomic Neuropathies

• Recently, three mutations in the tyrosine kinase domain of TRKA have been reported in patients with congenital insensitivity to pain with anhidrosis, which is an autosomal recessive disorder characterized by recurrent fever due to absence of sweating, no reaction to noxious stimuli, self-mutilating behavior, and mental retardation [6].

High impact information on Hereditary Sensory and Autonomic Neuropathies

• SPTLC1 is mutated in hereditary sensory neuropathy, type 1 [7].
• Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis [8].
• Hereditary sensory neuropathy is caused by a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4 ) gene [9].
• Furthermore, mutations in this lysine and in a histidine residue that is also predicted to be important for pyridoxal 5'-phosphate binding to Lcb2p also dominantly inactivate SPT similar to the hereditary sensory neuropathy type 1-like mutations in Lcb1p [10].
• Mutations in the yeast LCB1 and LCB2 genes, including those corresponding to the hereditary sensory neuropathy type I mutations, dominantly inactivate serine palmitoyltransferase [10].

Chemical compound and disease context of Hereditary Sensory and Autonomic Neuropathies

• Novel pathogenic mechanisms of congenital insensitivity to pain with anhidrosis genetic disorder unveiled by functional analysis of neurotrophic tyrosine receptor kinase type 1/nerve growth factor receptor mutations [11].
• Positive bethanechol chloride supersensitivity test in hereditary sensory neuropathy [12].
• Reduced substance P in hereditary sensory neuropathy in the mf rat [13].
• The histamine test reaction was positive, nerve biopsy and electrophysiological investigations confirmed sensory nerve involvement and the diagnosis of hereditary sensory neuropathy [14].

Biological context of Hereditary Sensory and Autonomic Neuropathies

• A novel point mutation affecting the tyrosine kinase domain of the TRKA gene in a family with congenital insensitivity to pain with anhidrosis [6].
• The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA) [15].
• Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis [15].
• Genetics of congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV. Clinical, biological and molecular aspects of mutations in TRKA(NTRK1) gene encoding the receptor tyrosine kinase for nerve growth factor [16].

Anatomical context of Hereditary Sensory and Autonomic Neuropathies

• A similar but larger increase was observed in peripheral nerves of mice affected with an hereditary sensory neuropathy, dystonia musculorum [17].
• There is pathological evidence that hereditary sensory radicular neuropathy (HSN type I) is a disorder related to multi-system atrophy with marked cell loss in the cerebral cortex, thalamus, brain stem and cerebellum [18].

Gene context of Hereditary Sensory and Autonomic Neuropathies

• Recently point mutations in the SPTLC1 subunit of serine palmitoyltransferase have been shown to cause the common form of dominant hereditary sensory neuropathy (HSN1) [19].
• Exclusion of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) as a common cause for hereditary sensory neuropathy [19].
• Exclusion of NFIL3 as the gene causing hereditary sensory neuropathy type I by mutation analysis [20].
• From its expression pattern and its chromosomal localization, PHF2 is a candidate gene for hereditary sensory neuropathy type I, HSN1 [21].
• Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA [22].

References