A homozygous frameshift mutation of sepiapterin reductase gene causing parkinsonism with onset in childhood

Lohmann, Ebba; Köroğlu, Çiğdem; Hanagasi, Hasmet A.; Dursun, Burcu; Taşan, Erşan; Tolun, Aslıhan

doi:10.1016/j.parkreldis.2011.10.001

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Volume 18, Issue 2 , Pages 191-193, February 2012

A homozygous frameshift mutation of sepiapterin reductase gene causing parkinsonism with onset in childhood

Ebba Lohmann
- Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34390, Turkey
- These authors contributed equally to this work.
Çiğdem Köroğlu
- Department of Molecular Biology and Genetics, KP 301, Boğaziçi University, Bebek, Istanbul 34342, Turkey
- These authors contributed equally to this work.
Hasmet A. Hanagasi
- Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34390, Turkey
Burcu Dursun
- Institute for Experimental Medicine, Istanbul University, Istanbul 34390, Turkey
Erşan Taşan
- Department of Computer Engineering, Boğaziçi University, Istanbul 34342, Turkey
Aslıhan Tolun
- Department of Molecular Biology and Genetics, KP 301, Boğaziçi University, Bebek, Istanbul 34342, Turkey
- Corresponding author. Tel.: +90 212 359 6472 (office), +90 533 433 0377 (GSM); fax: +90 212 287 2468 (office).

Received 2 August 2011; received in revised form 29 September 2011; accepted 1 October 2011. published online 24 October 2011.

Abstract

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.

Keywords: Sepiapterin reductase, Parkinsonism, Hypotonia