Expanding Phenotype of De Novo Mutations in GNAO1: Four New Cases and Review of Literature

David C. Schorling; Tobias Dietel; Christina Evers; Katrin Hinderhofer; Rudolf Korinthenberg; Daniel Ezzo; Carsten G. Bönnemann; Janbernd Kirschner

doi:10.1055/s-0037-1603977

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2017; 48(05): 371-377
DOI: 10.1055/s-0037-1603977

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Expanding Phenotype of De Novo Mutations in GNAO1: Four New Cases and Review of Literature

David C. Schorling

¹Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany

,

Tobias Dietel

²Epilepsy Centre Kork, Kehl-Kork, Germany

,

Christina Evers

³Institute of Human Genetics, Heidelberg University, Heidelberg, Germany

,

Katrin Hinderhofer

³Institute of Human Genetics, Heidelberg University, Heidelberg, Germany

,

Rudolf Korinthenberg

¹Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany

,

Daniel Ezzo

⁴Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, United States

,

Carsten G. Bönnemann

⁴Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, United States

,

Janbernd Kirschner

¹Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Freiburg, Germany

› Institutsangaben

Abstract

Mutations in GNAO1 (guanine nucleotide-binding protein, alpha-activating activity polypeptide O) were recently identified as being causative for early epileptic encephalopathy. Since then approximately 27 patients with severe developmental delay and different neurological phenotypes for epilepsy and involuntary movement disorder have been reported. We report four additional patients with mutations in GNAO1 including a report of siblings of different sex harboring the same de novo mutation (c.736G > A, p.Glu246Lys) but showing differences in phenotype with pronounced dystonia in the boy and epilepsy in his sister. Another de novo mutation in GNAO1 (c.607G > A, p.Gly203Arg) was identified in two unrelated girls with severe epilepsy. Both girls later also developed severe dystonia with severe nonepileptic spasms. An extensive review of published cases revealed that epilepsy was reported in only one male patient so far. Thus it appears possible that epilepsy is a sex-dependent phenotypic feature of GNAO1-related diseases.

Keywords

early infantile epileptic encephalopathy - Othahara syndrome - GNAO1 mutation - movement disorders - sex-dependent phenotype

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Referenzen

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