ARL6IP1 mutation causes congenital insensivity to pain, self-mutilation and spastic paraplegia

ABSTRACT

Hereditary sensory 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, self-mutilation, and spastic paraplegia. Whole exome sequencing showed a homozygous frameshift variant c.[577_580del], p.(Lys193Phefs*37) in ARL6IP1. The protein harbours 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.

Graphical Abstract

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