A homozygous frameshift mutation of sepiapterin reductase gene causing parkinsonism with onset in childhood.
We report two siblings that presented hypotonia and very early-onset parkinsonism. Homozygosity mapping using SNP genome scan data identified a candidate locus that was 12.2 Mega base pairs. By exome sequencing, we found a homozygous five-nucleotide deletion (c.448_452delAGAAC) in gene Sepiapterin Reductase (SPR). The mutation is predicted to lead to premature translational termination. Sepiapterin reductase deficiency (SRD) is a recently recognized dopa-responsive dystonia. Our findings show that SRD can manifest as early-onset parkinsonism, widening the spectrum of the disease phenotype and adding to the genetic heterogeneity of the disease.
Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34390, Turkey.
Ebba
E
Lohmann
Çiğdem
Ç
Köroğlu
Hasmet A
HA
Hanagasi
Burcu
B
Dursun
Erşan
E
Taşan
Aslıhan
A
Tolun
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D002648:Child; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics*
D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase