A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome.
Mutations in the potassium channel-related gene KCTD7 were described so far in a single family with progressive myoclonus epilepsy. We describe a unique phenotype: acute onset of myoclonus and ataxia, associated with abnormal opsoclonus-like eye movements; improvement of clinical symptoms under steroid treatment; and appearance of epileptic activity on EEG 2 years later without overt seizures. After excluding possible genetic causes, whole-genome exome sequencing was performed in order to identify the causative gene. One heterozygous missense mutation (R84W) was detected by exome sequencing and a large heterozygous deletion of exons 3 and 4 by MLPA analysis. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. The mutation affects a highly conserved segment of the predicted protein, changing a basic amino acid into neutral. The large deletion probably results in a truncated protein. The different phenotype broadens the spectrum of KCTD7-related diseases. Therefore, patients diagnosed as having opsoclonus-myoclonus with an atypical course should be evaluated for KCTD7 mutations.
Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
Lubov
L
Blumkin
Sara
S
Kivity
Dorit
D
Lev
Sarit
S
Cohen
Ruth
R
Shomrat
Tally
T
Lerman-Sagie
Esther
E
Leshinsky-Silver
D000595:Amino Acid Sequence; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D053578:Opsoclonus-Myoclonus Syndrome / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*
C522280:KCTD7 protein, human; D015221:Potassium Channels