De novo p.Glu61Ter mutation in GCH1 in a Moroccan patient with dopa-responsive dystonia: a case report

Abstract

Dopa-responsive dystonia (DRD) is a hereditary movement disorder due to a selective nigrostriatal dopamine deficiency. It is characterized by onset in childhood or adolescence with marked diurnal fluctuation with or without Parkinsonian features, and is caused by mutations in GCH1 gene. We report in this study the clinical and genetic features of the first DRD Moroccan patient. Using a gene panel sequencing, we identified a heterozygous nonsense variant p. Glu61Ter in GCH1. A subsequent targeted segregation analysis by Sanger sequencing validated the presence of the mutation in the patient, which was found to have occurred de novo. The objective of this study is to report the first description of DRD in Morocco, and highlights the importance of new generation sequencing technology in the reduction of medical wandering and the management of hereditary diseases.

Keywords: Dopa-responsive dystonia; GCH1 gene; case report; de novo non-sense mutation.

Figure 1

pedigree of the studied family (A); darkened square indicates the patient with dopa-responsive dystonia and hatched squares and circles indicate males and females with essential tremor; arrow: index patient; asterisk: genetic testing performed; sanger sequencing confirms the presence of the c.181G>T mutation in GCH1 in heterozygous state (B); partial nucleotide sequence alignment of human GCH1 with orthologs shows evolutionary conservation between species of the nucleotide 181 and the codon 61 (C)