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

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.

• Authors: Ebba Lohmann, Çiğdem Köroğlu, Hasmet A Hanagasi, Burcu Dursun, Erşan Taşan, Aslıhan Tolun
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 18 Issue 2 Pg. 191-3 (Feb 2012) ISSN: 1873-5126 [Electronic] England
• PMID: 22018912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Alcohol Oxidoreductases
• sepiapterin reductase

Topics

• Adolescent
• Adult
• Age Factors
• Alcohol Oxidoreductases (genetics)
• Child
• Female
• Frameshift Mutation
• Gene Deletion
• Homozygote
• Humans
• Male
• Middle Aged
• Parkinsonian Disorders (diagnosis, genetics)