Phenotype analysis of the families with Gerstmann-Str?ussler-Scheinker syndrome caused by prion protein gene mutations / 中华神经科杂志

ABSTRACT

Objective:To explore the clinical, imaging features and pathogenic mutations in three cases of Gerstmann-Str?ussler-Scheinker syndrome (GSS) with ataxia.Methods:Since 2014, totally 137 probands with autosomal dominant or sporadic ataxia were treated in the Department of Neurology, China-Japan Friendship Hospital. They were screened for mutations in prion protein (PRNP) gene using next-generation sequencing. Spinocerebellar ataxia 1, 2, 3, 6, 7, 8, 12, 17 and dentatorubral-pallidoluysian atrophy were excluded by capillary electrophoresis. Potential pathogenic variants were confirmed by Sanger sequencing. Pathogenicity assessment was interpreted according to the American College of Medical Genetics standards and guidelines. Clinical phenotypes and imaging features of patients were analyzed in detail.Results:Three pedigrees of GSS caused by PRNP gene variants were found. The probands of three pedigrees carried reported heterozygous missense mutation c.305C>T (p.P102L), all onset in adults. All of the three probands showed walking instability and dysarthria, additionally, the proband of pedigree 1 showed parkinsonian signs, the proband of pedigree 2 had cognitive impairment. Brain magnetic resonance imaging showed cerebellar atrophy of different degrees in probands 2 and 3, while pallidum hyperintense signal in proband 1.Conclusions:GSS as a rare subtype of prion disease, could be characterized by cerebellar ataxia. For patients with ataxia, attention should be paid to GSS disease-causing gene mutations in genetic testing. Early diagnosis based on genetic testing will be instrumental in genetic counseling and birth defect intervention in pedigree members.