DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability


Koroglu C., BAYSAL L., Cetinkaya M., KARASOY H. , Tolun A.

PARKINSONISM & RELATED DISORDERS, cilt.19, ss.320-324, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 19 Konu: 3
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1016/j.parkreldis.2012.11.006
  • Dergi Adı: PARKINSONISM & RELATED DISORDERS
  • Sayfa Sayıları: ss.320-324

Özet

Familial parkinson's disease is both clinically and genetically heterogeneous. By mapping the disease locus with a lod score of 5.13 to a < 3.5 Mbp region at 1p31.3 in a consanguineous family and subsequent exome sequencing analysis, we identified homozygous truncating mutation p.Q734X in DNAJC6. Four members of the family were afflicted with juvenile parkinsonism that presented with mental retardation, pyramidal signs and epilepsy, as well as varying degrees of a progressive neurological disease. Recently a splicing mutation in the same gene was reported in two brothers with juvenile parkinsonism that was not L-Dopa responsive and not accompanied by pyramidal signs or mental retardation. Also, an 80-kb deletion that included DNAJC6 sequences was identified in a boy reported as having obesity, epilepsy and mental retardation but not any signs of parkinsonism. The phenotype of our study family resembles both of those families, which among themselves do not share any clinical features. Our findings further establish DNAJC6 as a juvenile parkinsonism gene, and expand the spectrums of the parkinsonism phenotype and DNAJC6 mutation.