Challenging Diagnosis of a Patient with Two Novel Variants in the SYNE1 Gene

Int J Mol Sci. 2024 Oct 9;25(19):10841. doi: 10.3390/ijms251910841.

Abstract

We report a case of SYNE1-associated autosomal recessive spinocerebellar ataxia (SCAR8) presenting with a complex multisystemic phenotype, including highly elevated creatine kinase levels and lower-leg muscle atrophy. In addition to identifying two novel pathogenic variants in the SYNE1 gene, whole-exome sequencing revealed three variants of uncertain significance in the DYSF gene. Electromyography and muscle magnetic resonance imaging indicated a neurogenic pattern of muscle involvement. These findings, along with the segregation analysis of the variants, allowed us to exclude DYSF-associated muscular dystrophy; however, we cannot entirely rule out the possibility that the DYSF gene variants may act as modifiers of the patient's phenotype.

Keywords: SYNE1; ataxia; hyperCKemia; neuropathy.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Cytoskeletal Proteins* / genetics
  • Electromyography
  • Exome Sequencing
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Nerve Tissue Proteins* / genetics
  • Nuclear Proteins* / genetics
  • Pedigree
  • Phenotype
  • Spinocerebellar Ataxias / congenital
  • Spinocerebellar Ataxias / diagnosis
  • Spinocerebellar Ataxias / diagnostic imaging
  • Spinocerebellar Ataxias / genetics

Substances

  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • SYNE1 protein, human