Mitochondrial complex I NUBPL mutations cause combined dystonia with bilateral striatal necrosis and cerebellar atrophy.

ABSTRACT:

Background and purpose

The recent advances in genetics have helped to unravel the cause of many dystonia syndromes. With the broadening spectrum of genetically defined dystonia syndromes, distinct clinico-radiological phenotypes are a welcome handle to guide the diagnostic work-up.

Methods

Exome sequencing was used to elucidate the genetic cause of a syndrome characterized by generalized dystonia, pyramidal and cerebellar involvement, with bilateral striatal necrosis (BSN) and cerebellar atrophy on magnetic resonance imaging. Homozygosity mapping and linkage analysis were used in a supportive role. Known genetic causes of BSN were excluded by use of exome data or Sanger sequencing.

Results

Compound heterozygous mutations were identified in the NUBPL gene in a small UK kindred. The gene lay in a region of positive linkage and segregated with disease in a family of six individuals.

Conclusion

NUBPL mutations cause early onset, autosomal recessive generalized dystonia with cerebellar ataxia, pyramidal signs, preserved cognition and a distinct magnetic resonance imaging appearance with BSN and cerebellar atrophy.

SUBMITTER: Balint B 

PROVIDER: S-EPMC6767441 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature