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

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

doi:10.1016/j.parkreldis.2011.10.001

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

Parkinsonism Relat Disord. 2012 Feb;18(2):191-3. doi: 10.1016/j.parkreldis.2011.10.001. Epub 2011 Oct 21.

Authors

Ebba Lohmann¹, Çiğdem Köroğlu, Hasmet A Hanagasi, Burcu Dursun, Erşan Taşan, Aslıhan Tolun

Affiliation

¹ Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34390, Turkey.

PMID: 22018912
DOI: 10.1016/j.parkreldis.2011.10.001

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age Factors
Alcohol Oxidoreductases / genetics*
Child
Female
Frameshift Mutation*
Gene Deletion*
Homozygote*
Humans
Male
Middle Aged
Parkinsonian Disorders / diagnosis
Parkinsonian Disorders / genetics*

Substances

Alcohol Oxidoreductases
sepiapterin reductase