講演情報
[O27-5]新規のATP1A3バリアントにより運動障害を呈した2症例
○古川 省悟1, 宮本 祥子1, 福村 忍2, 久保田 一生3, 多賀 俊明4, 中島 光子1, 才津 浩智1 (1.浜松医科大学 医化学講座, 2.札幌医科大学 小児科, 3.岐阜大学 大学院医学系研究科 小児科学教室, 4.市立長浜病院 小児科)
【Background】ATP1A3 (NM_152296.5) encodes a subunit of Na+/K+-ATPase transmembrane ion pump. Heterozygous variants in ATP1A3 cause rapid-onset dystonia parkinsonism (OMIM # 128235), alternating hemiplegia of childhood (# 614820), CAPOS syndrome (# 601338), and polymicrogyria.
【Patients】Patient 1 is a 1-year-old Japanese girl presented developmental delay, hypotonia, foot clonus, hyperreflexia of the patellar tendon and the Achilles tendon. Alternating paralysis, seizures, and involuntary movements are absent. Brain magnetic resonance imaging (MRI) showed hypoplasia of the brainstem. Patient 2 is a 14-year-old Japanese boy who showed progressive paroxysmal dystonia. His mother and maternal grandfather also showed mild adult-onset dystonia of the upper extremities.
【Results】Exome sequencing revealed two novel heterozygous ATP1A3 variants. Patient 1 had a de novo c.2408G＞A, p.(Gly803Asp) variant located at exon 17 in the transmembrane region of ATP1A3 clustering the AHC-associated variants. Patient 2 had an indel c.2672_2688+10delinsCAG variant. His affected mother and unaffected elder brother also had the same variant. The mRNA analysis revealed that this variant caused in-frame indel alteration at the Ser891_Trp896 residue located at the extracellular region of ATP1A3.
【Conclusion】The genotype-phenotype correlation and penetrance of ATP1A3-related disorders are variable. We described the onset time and specific symptoms or severity for each individual and presented an example of intrafamilial variability of ATP1A3-related disorders.
【Patients】Patient 1 is a 1-year-old Japanese girl presented developmental delay, hypotonia, foot clonus, hyperreflexia of the patellar tendon and the Achilles tendon. Alternating paralysis, seizures, and involuntary movements are absent. Brain magnetic resonance imaging (MRI) showed hypoplasia of the brainstem. Patient 2 is a 14-year-old Japanese boy who showed progressive paroxysmal dystonia. His mother and maternal grandfather also showed mild adult-onset dystonia of the upper extremities.
【Results】Exome sequencing revealed two novel heterozygous ATP1A3 variants. Patient 1 had a de novo c.2408G＞A, p.(Gly803Asp) variant located at exon 17 in the transmembrane region of ATP1A3 clustering the AHC-associated variants. Patient 2 had an indel c.2672_2688+10delinsCAG variant. His affected mother and unaffected elder brother also had the same variant. The mRNA analysis revealed that this variant caused in-frame indel alteration at the Ser891_Trp896 residue located at the extracellular region of ATP1A3.
【Conclusion】The genotype-phenotype correlation and penetrance of ATP1A3-related disorders are variable. We described the onset time and specific symptoms or severity for each individual and presented an example of intrafamilial variability of ATP1A3-related disorders.