Familial periodic cerebellar ataxia without myokymia maps to a 19-cM region on 19p13

Am J Hum Genet. 1995 Jun;56(6):1443-9.

Abstract

Familial periodic cerebellar ataxia (FPCA) is a heterogeneous group of rare autosomal dominant disorders characterized by episodic cerebellar disturbance. A potassium-channel gene (KCNA1) has been found to be responsible for one of its subgroups, familial periodic cerebellar ataxia with myokymia (FPCA/+M; MIM 160120). A different subgroup that is not associated with myokymia (FPCA/-M; MIM 108500) was recently mapped to chromosome 19p. Here we have performed linkage analysis in two large families with FPCA/-M that also demonstrated neurodegenerative pathology of the cerebellum. Three markers in 19p13 gave significant lod scores (> 3.0), while linkage to KCNA1 and three known loci for spinocerebellar ataxia (SCA1, SCA2, and SCA3) was excluded. The highest lod score was obtained with the marker D19S413 (4.4 at recombination fraction 0), and identification of meiotic recombinants in affected individuals placed the locus between the flanking markers D19S406 and D19S226, narrowing the interval to 19 cM. A CAG trinucleotide-repeat expansion was detected in one family but did not cosegregate with the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cerebellar Ataxia / classification
  • Cerebellar Ataxia / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19 / genetics*
  • Fasciculation
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Genome, Human
  • Humans
  • Kv1.1 Potassium Channel
  • Male
  • Meiosis
  • Pedigree
  • Periodicity
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • Repetitive Sequences, Nucleic Acid
  • Spinocerebellar Degenerations / genetics

Substances

  • Genetic Markers
  • KCNA1 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Kv1.1 Potassium Channel