Novel mutations in FLVCR1 cause tremors, sensory neuropathy with retinitis pigmentosa

Abstract

The mutations of the feline leukemia virus subgroup C receptor‐related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1‐associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well‐recognized features of FLVCR1‐associated disease, tremor is rarely described. Whole‐exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient.

Biallelic variation in the choline and ethanolamine transporterFLVCR1underlies a pleiotropic disease spectrum from adult neurodegeneration to severe developmental disorders

“…2 ). In Family 18, the young adult asymptomatic sister of Individual 25 was also homozygous for FLVCR1 : c.502C>G p.L168V; as age of onset as late as the third or fourth decade of life has been described, this likely represents age-related penetrance 28 .…”

Unearthing FLVCR1a: tracing the path to a vital cellular transporter

“…This degeneration leads to progressive vision loss, sensory ataxia, and, in some cases, a lack of pain sensitivity. Additionally, variable features of these FLVCR1-related diseases encompass conditions such as scoliosis, camptodactyly, achalasia, gastrointestinal dysmotility [ 61 , 72 ], as well as tremors [ 73 ], learning disabilities, and developmental delays [ 74 ]. Remarkably, erythropoiesis is not compromised in these patients.…”