Table 1.

Summary of Molecular Genetic Testing Used in GTPCH1-Deficient DRD

Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
GCH1Sequence analysis 2~60% (20%-80%) 3
Deletion/duplication analysis 4~5%-10% 5
Unknown 6NA

See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


In genetic reports on DRD, in which conventional genomic DNA sequencing of GCH1 was conducted in a relatively large number of families, pathogenic variants in the coding region (including the splice sites) of this gene were found in ~60% (mean) of DRD pedigrees. Mutation detection rate by sequence analysis ranged from 20% [Skrygan et al 2001] to 80% [Furukawa 2003, Segawa et al 2003, Hagenah et al 2005].


Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


After conducting GCH1 analysis that included both sequence analysis and deletion/duplication analyses, Furukawa [2004], Hagenah et al [2005], and Clot et al [2009] identified GCH1 pathogenic variants in 80%-90% of the families with DRD. Zirn et al [2008] found GCH1 pathogenic variants in 62% (54% with single nucleotide variants and 8% with exon deletions) of individuals with clinically confirmed DRD.


For information on locus heterogeneity in DRD, see Nomenclature and Differential Diagnosis.

From: GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia

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