講演情報
[O25-1]DBSによって運動障害の改善がみられたGNAO1のイントロンバリアントが同定された症例
○宮本 祥子1, 中島 光子1, 福村 忍2, 熊田 聡子3, 才津 浩智1 (1.浜松医科大学 医学部 医化学講座, 2.札幌医科大学 医学部 小児科, 3.東京都立神経病院 神経小児科)
【Background】GNAO1 variants are associated with a wide range of neurodevelopmental disorders including epileptic encephalopathies and movement disorders. It has been reported that dominant negative GNAO1 variants are associated with movement disorders, and the 207-246 amino acid region was proposed as a mutational hotspot.【Patient】A 14 years old Japanese girl showed psychomotor developmental delay and juvenile parkinsonism-like symptoms including postural instability, gait disturbance and dysarthria. At 12 years of age, deep brain stimulation (DBS) of the bilateral globus pallidus interna was performed and her oral intake and walking ability were recovered.【Results】Whole exome sequencing identified an intronic variant (NM_020988.3:c.724-8G＞A) in GNAO1 which was segregated from her asymptomatic mother who possessed the variant as low-prevalence somatic mosaicism. Using RNA extracted from lymphoblastoid cells derived from the patient, we demonstrated that the variant caused abnormal splicing of in-frame 6-bp intronic retention, leading to 2 amino acid insertion (p.Thr241_Asn242insProGln). Immunoblot analysis showed that there was no significant difference in expression level of our mutant compared to dominant negative (DN) mutant. Immunostaining showed that DN mutant was clearly localized in the cell periphery, whereas our mutant showed similar pattern to that of DN, but its localization was partially shifted to the cytoplasm.【Conclusion】Our report highlighted importance of genetic analysis in terms of the selection of clinical treatment as well as genetic counseling.