FLVCR1-related disease as a rare cause of retinitis pigmentosa and hereditary sensory autonomic neuropathy

Eur J Med Genet. 2020 Nov;63(11):104037. doi: 10.1016/j.ejmg.2020.104037. Epub 2020 Aug 19.

Abstract

FLVCR1 encodes for a transmembrane heme exporter protein and it is known to cause a rare form of syndromic retinitis pigmentosa: posterior column ataxia with retinitis pigmentosa. Recently, the FLVCR1-associated phenotype has been expanded with sporadic reports of hereditary sensory-autonomic neuropathy or non-syndromic retinitis pigmentosa. Here, we report a 23-year- old female with early onset hypomyelinating sensory-autonomic neuropathy and retinitis pigmentosa. Both features were present since childhood. The patient developed signs of advanced retinitis pigmentosa by the age of 10 years leading to legal blindness after the age of 18. Following candidate gene panel testing, which was negative, whole exome sequencing revealed compound heterozygous pathogenic FLVCR1 variants: NM_014053.3: c.3G > T; p.(Met1?) and NM_014053.3: c.730G > A; p.(Gly244Ser), the latter variant is novel. In this report we highlight the association of retinitis pigmentosa with hypomyelinating sensory-autonomic neuropathy, which could be underdiagnosed due to variable severity. To summarize, the phenotypic heterogeneity of FLVCR1 variants is broad and should include retinitis pigmentosa along with range of neurological features.

Keywords: FLVCR1 gene; Hereditary sensory-autonomic neuropathy; Hypomyelinating neuropathy; Posterior column ataxia with retinitis pigmentosa; Retinitis pigmentosa.

Publication types

  • Case Reports

MeSH terms

  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / pathology
  • Female
  • Hereditary Sensory and Autonomic Neuropathies / genetics*
  • Hereditary Sensory and Autonomic Neuropathies / pathology
  • Humans
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics*
  • Mutation
  • Phenotype
  • Protein Domains
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics*
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology
  • Young Adult

Substances

  • FLVCR1 protein, human
  • Membrane Transport Proteins
  • Receptors, Virus