ARL6IP1 mutation causes congenital insensitivity to pain, acromutilation and spastic paraplegia

Clin Genet. 2018 Jan;93(1):169-172. doi: 10.1111/cge.13048. Epub 2017 Aug 31.

Abstract

Hereditary sensory and autonomic neuropathies (HSAN) type II are characterized by autosomal recessive inheritance, onset at birth and self-mutilating behavior. Here, we described a new patient with congenital insensitivity to pain, sensory neuropathy, acromutilation, and spastic paraplegia. Whole-exome sequencing showed a homozygous frameshift variant c.[577_580del], p.(Lys193Phefs*37) in ARL6IP1. The protein harbors reticulon-like short hairpin transmembrane domains and has a role in endoplasmic reticulum shaping. The variant causes an additional C-terminus hydrophobic domain which could disrupt its function. ARL6IP1 interacts with atlastin-1 responsible for SPG3A and HSAN type ID. This report highlights the role of ARL6IP1 in the pathophysiology of insensitivity to pain and spastic paraplegia.

Keywords: ARL6IP1; congenital insensitivity to pain; hereditary sensory neuropathy.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Exome Sequencing / methods
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Hereditary Sensory and Autonomic Neuropathies / genetics*
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Pain Insensitivity, Congenital / genetics*
  • Paraplegia / genetics*
  • Pedigree

Substances

  • ARL6IP1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins