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ARL6IP1 mutation causes congenital insensitivity to pain, acromutilation and spastic paraplegia
Author(s) -
Nizon M.,
Küry S.,
Péréon Y.,
Besnard T.,
Quinquis D.,
Boisseau P.,
Marsaud T.,
Magot A.,
Mussini J.M.,
Mayrargue E.,
Barbarot S.,
Bézieau S.,
Isidor B.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13048
Subject(s) - hereditary spastic paraplegia , frameshift mutation , paraplegia , exome sequencing , spastic , mutation , spasticity , medicine , endoplasmic reticulum , genetics , neuroscience , biology , spinal cord , physical medicine and rehabilitation , gene , phenotype , cerebral palsy
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.