Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1

BMC Med Genet. 2015 Aug 19:16:61. doi: 10.1186/s12881-015-0213-y.

Abstract

Background: Ataxia with oculomotor apraxia type 1 is an autosomal-recessive neurodegenerative disorder characterized by a childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. Ataxia with oculomotor apraxia type 1 is caused by bi-allelic mutations in APTX (chromosome 9p21.1).

Case presentation: Our patient has a clinical presentation that is typical for ataxia with oculomotor apraxia type 1 with no particularly severe phenotype. Multiplex Ligation-dependent Probe Amplification analysis resulted in the identification of a homozygous deletion of all coding APTX exons (3 to 9). SNP array analysis using the Illumina Infinium CytoSNP-850 K microarray indicated that the deletion was about 62 kb. Based on the SNP array results, the breakpoints were found using direct sequence analysis: c.-5 + 1225_*44991del67512, p.0?. Both parents were heterozygous for the deletion. Homozygous complete APTX deletions have been described in literature for two other patients. We obtained a sample from one of these two patients and characterized the deletion (156 kb) as c.-23729_*115366del155489, p.0?, including the non-coding exons 1A and 2 of APTX. The more severe phenotype reported for this patient is not observed in our patient. It remains unclear whether the larger size of the deletion (156 kb vs 62 kb) plays a role in the phenotype (no extra genes are deleted).

Conclusion: Here we described an ataxia with oculomotor apraxia type 1 patient who has a homozygous deletion of the complete coding region of APTX. In contrast to the patient with the large deletion, our patient does not have a severe phenotype. More patients with deletions of APTX are required to investigate a genotype-phenotype effect.

Publication types

  • Case Reports

MeSH terms

  • Base Sequence
  • DNA-Binding Proteins / deficiency*
  • Electromyography
  • Gene Deletion
  • Humans
  • Male
  • Microarray Analysis
  • Molecular Sequence Data
  • Marokko
  • Nuclear Proteins / deficiency*
  • Phenotype*
  • Polymorphism, Single Nucleotide / genetics
  • Sequence Analysis, DNA
  • Spinocerebellar Ataxias / congenital
  • Spinocerebellar Degenerations / genetics*

Substances

  • APTX protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins

Supplementary concepts

  • Spinocerebellar ataxia, autosomal recessive 1