1. Genotype-phenotype correlations in alternating hemiplegia of childhood
- Author
-
Ryutaro Kira, Hidee Arai, Toshio Ikeda, Hirokazu Oguni, Shinichi Hirose, Tomoyuki Akiyama, Sadami Kimura, Atsushi Araki, Seiro Narumiya, Takeshi Yoshida, Hisashi Kawawaki, Kazumoto Iijima, Masayuki Shimono, Yoshinobu Oyazato, Atsushi Ishii, Shininchi Hirabayashi, Shiro Ozasa, Sunao Dejima, Shuichi Tsuneishi, Masayuki Sasaki, Yuko Tanabe, Bo Zhang, Shoji Tsuji, Yoichiro Oda, Sumimasa Yamashita, Tsukasa Ohashi, Yoshiaki Saito, Kenji Yokochi, Motomasa Suzuki, Hiroshi Ichiseki, Nobuyuki Kishi, Naoya Morisada, Akihiro Yasuhara, and Satoshi Takada
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Pediatrics ,Heterozygote ,Adolescent ,Gross motor skill ,Mutation, Missense ,Hemiplegia ,Neonatal onset ,Severity of Illness Index ,symbols.namesake ,Young Adult ,Status Epilepticus ,ATP1A3 ,Genotype ,medicine ,Missense mutation ,Humans ,Child ,Flunarizine ,Genetic Association Studies ,Sanger sequencing ,business.industry ,Alternating hemiplegia of childhood ,Infant ,medicine.disease ,Respiratory Paralysis ,Motor Skills Disorders ,Child, Preschool ,symbols ,Female ,Neurology (clinical) ,Sodium-Potassium-Exchanging ATPase ,business ,medicine.drug - Abstract
Objective: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype–phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. Methods: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. Results: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3 : Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. Conclusions: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.
- Published
- 2014