Variant in SCYL1 gene causes aberrant splicing in a family with cerebellar ataxia, recurrent episodes of liver failure, and growth retardation

Eur J Hum Genet. 2019 Feb;27(2):263-268. doi: 10.1038/s41431-018-0268-2. Epub 2018 Sep 26.


Herein, we describe two members of one family who presented with recurrent episodes of hepatic failure, cerebellar ataxia, peripheral neuropathy, and short stature. Liver transplantation was considered. Whole-exome sequencing (Trio) revealed a synonymous variant in exon 4 of SCYL1:c.459C>T p. (Gly153Gly), which did not appear to affect the protein sequence. Computational prediction analysis suggested that this modification could alter the SCYL1 mRNA splicing processing to create a premature termination codon. The SCYL1 mRNAs in our patient's lymphocytes were analyzed and aberrant splicing was found. Molecular analysis of family members identified the parents as heterozygous recessive carriers and the proband as well as an affected aunt as homozygous. Evidently, harmless synonymous variants in the SCYL1 gene can damage gene splicing and hence the expression. We confirmed that the pathogenicity of this variant in the SCYL1 gene was associated with spinocerebellar ataxia, autosomal recessive 21 (SCAR21). Other reported cases (accept one) of liver failure found in the SCYL1 variants resolved during childhood, therefore orthotropic liver transplantation was no longer appropriate.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Adolescent
  • Cerebellar Ataxia / genetics
  • Cerebellar Ataxia / pathology
  • Child, Preschool
  • Codon, Terminator
  • DNA-Binding Proteins
  • Female
  • Growth Disorders / genetics*
  • Growth Disorders / pathology
  • Humans
  • Liver Failure / genetics*
  • Liver Failure / pathology
  • Male
  • Mutation
  • Pedigree
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / pathology
  • RNA Splicing*
  • Syndrome
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Codon, Terminator
  • DNA-Binding Proteins
  • SCYL1 protein, human
  • Transcription Factors