Further supporting evidence for REEP1 phenotypic and allelic heterogeneity

摘要

Heterozygous mutations in REEP1 (MIM #609139) encoding the receptor expressionenhancing protein 1 (REEP1) are a well-recognized and relatively frequent cause of autosomaldominant hereditary spastic paraplegia (HSP), SPG31.1 REEP1 localizes in the mitochondriaand endoplasmic reticulum (ER) and facilitates ER-mitochondria interactions.2 In addition tothe HSP phenotype, REEP1 has been associated with an autosomal dominant spinal type ofCharcot-Marie-Tooth disease in 2 families.3 More recently, a patient with homozygous REEP1mutation with a much more severe phenotype akin to spinal muscular atrophy with respiratorydistress type 1 (SMARD1) was reported.4 In this report, we present a patient with a homozygousmutation in REEP1 manifesting a severe congenital distal spinal muscular atrophy (SMA) withdiaphragmatic paralysis, expanding the phenotype from mild autosomal dominant HSP throughto severe recessive distal SMA pattern.