Details of Disease

General Information of Disease (ID: DISNE3R5)

• Disease Name: Hereditary sensory and autonomic neuropathy type 4
• Synonyms: neuropathy, congenital sensory, with anhidrosis; hereditary sensory and autonomic neuropathy 4; HSNAN4; hereditary sensory neuropathy type 4; HSAN IV; CIPA; HSAN 4; familial dysautonomia, type 2; hereditary sensory and autonomic neuropathy type IV; Hereditary Sensory and Autonomic Neuropathy Type IV; NTRK1 hereditary sensory and autonomic neuropathy; congenital insensitivity to pain with anhidrosis; insensitivity to pain, congenital, with anhidrosis; hereditary sensory neuropathy type IV; hereditary sensory and autonomic neuropathy caused by mutation in NTRK1; congenital insensitivity to pain-anhidrosis syndrome; HSAN4; CIP-anhidrosis syndrome
• Definition: Hereditary sensory and autonomic neuropathy, type 4 (HSAN4) is an inherited disorder characterized by anhidrosis, insensitivity to pain, self-mutilating behavior and episodes of fever.
• Disease Hierarchy:
  DIS2VOAM: Hereditary sensory and autonomic neuropathy
  DISNE3R5: Hereditary sensory and autonomic neuropathy type 4
• Disease Identifiers:
  MONDO ID: MONDO_0009746
  MESH ID: D009477
  UMLS CUI: C0020074
  OMIM ID: 256800
  MedGen ID: 6915
  Orphanet ID: 642
  SNOMED CT ID: 62985007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NTRK1	TTTDVOJ	Limited	Genetic Variation	[1]
PKLR	TT31N4S	Limited	Genetic Variation	[2]
DNMT1	TT6S2FE	Strong	Biomarker	[3]
NGFR	TTEDJN4	Strong	Genetic Variation	[4]
NTRK1	TTTDVOJ	Definitive	Autosomal recessive	[5]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NDN	OTYBYJ82	Strong	Biomarker	[6]
NTRK1	OTJORQAU	Definitive	Autosomal recessive	[5]
RETREG1	OTYOSLZX	Definitive	Biomarker	[7]

References

• [1] Heterotopic ossifications and Charcot joints: Congenital insensitivity to pain with anhidrosis (CIPA) and a novel NTRK1 gene mutation.Eur J Med Genet. 2020 Jan;63(1):103613. doi: 10.1016/j.ejmg.2019.01.003. Epub 2019 Jan 21.
• [2] Congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency.Hum Mutat. 2001 Oct;18(4):308-18. doi: 10.1002/humu.1192.
• [3] Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011 Jun;43(6):595-600. doi: 10.1038/ng.830. Epub 2011 May 1.
• [4] Mutations in TrkA Causing Congenital Insensitivity to Pain with Anhidrosis (CIPA) Induce Misfolding, Aggregation, and Mutation-dependent Neurodegeneration by Dysfunction of the Autophagic Flux.J Biol Chem. 2016 Oct 7;291(41):21363-21374. doi: 10.1074/jbc.M116.722587. Epub 2016 Aug 22.
• [5] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [6] Novel NTRK1 Frameshift Mutation in Congenital Insensitivity to Pain With Anhidrosis.J Child Neurol. 2015 Sep;30(10):1357-61. doi: 10.1177/0883073814552438. Epub 2014 Oct 14.
• [7] Mutations in FAM134B, encoding a newly identified Golgi protein, cause severe sensory and autonomic neuropathy. Nat Genet. 2009 Nov;41(11):1179-81. doi: 10.1038/ng.464. Epub 2009 Oct 18.