A new mutation of GCH1 in triplets family with dopa-responsive dystonia


Nobutada Tachi, School of Health Sciences, Sapporo Medical University, S1 W16 Chuo-ku, 060-8556 Sapporo, Japan (tel.: +11 611 2111; fax: +11 611 2155; e-mail: tati@sapmed.ac.jp).


Background:  Dopa-responsive dystonia (DRD) is associated with mutations of the GCH1. We first report four female siblings with DRD from one family, including three monozygotic triplets patients clinically and genetically.

Methods:  We performed GCH1 analysis by direct sequencing of PCR product amplified with primers designed to cover the entire exons of GCH1 in those four patients and their mother.

Results:  In all four patients with DRD, a new frameshift mutation (c.729delG; p.A190fsX191) was identified in the exon 5 of GCH1.

Conclusions:  The frameshift mutation results in truncated GCH1 protein which is suspected to result in loss of function of the catalytic GTP-cyclohydrol domain.