Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2

Neurol Sci. 2013 Sep;34(9):1629-32. doi: 10.1007/s10072-013-1298-8. Epub 2013 Jan 24.

Abstract

Anticipation is a phenomenon characterized by decreasing age at onset and increasing severity of symptoms of a disease in successive generations within a pedigree. Anticipation mostly occurs in neurodegenerative diseases with expansion of unstable trinucleotide repeats. However, it has not been previously pointed out in episodic ataxia type 2 (EA2). Clinical and genetic analyses were performed in nine members from three consecutive generations of a Korean family with EA2. We performed a polymerase chain reaction (PCR)-based direct sequence analysis of all coding regions of CACNA1A using genomic DNA. The clinically affected family members showed recurrent vertigo, interictal nystagmus, and childhood epilepsy. There is a decrease in the age onset (possible genetic anticipation) in three succeeding generations of the family. Genetic analysis identified a splice site mutation (p.Val1465Glyfs13X) and normal trinucleotide repeats in CACNA1A in all clinically affected and one unaffected members. Recognizing anticipation would aid in genetic counseling in EA2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Anticipation, Genetic / genetics*
  • Asian People / genetics
  • Ataxia / genetics*
  • Calcium Channels / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Nystagmus, Pathologic / genetics*
  • Pedigree
  • RNA Splice Sites
  • Trinucleotide Repeats / genetics
  • Young Adult

Substances

  • CACNA1A protein, human
  • Calcium Channels
  • RNA Splice Sites

Supplementary concepts

  • Episodic Ataxia, Type 2