Novel heterozygous variant of ADPRHL2 causes pathogenic variation in CONDSIAS
Shuang Yan,
Jie Ren,
Hongting Su,
Jiehui Ma,
Weijie He,
Xiaofang Cai,
Dan Sun
Affiliations
Shuang Yan
Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Jie Ren
Department of Emergency and Critical Care Center, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Hongting Su
Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Jiehui Ma
Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Weijie He
Aegicare (Shenzhen) Technology Co., Ltd., Shenzhen, China
Xiaofang Cai
Department of Emergency and Critical Care Center, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China; Corresponding author.
Dan Sun
Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China; Corresponding author.
Adprhl2 (OMIM: 610624) mutation associated stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, OMIM: 618170) is a sporadic neurodegenerative disease with poor prognosis. ADPRHL2 encodes ADP-ribosylhydrolase 3 (ARH3), which participates in ADP-ribosylation to remove poly-ADP ribose (PAR). We found a new compound heterozygous mutation in the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A in a 30-month-old boy, who showed gait instability, abnormal EEG, and developmental delay after respiratory infection. He died of convulsions 4 months after onset. By constructing a mutant plasmid and using Western blot to detect the expression of ARH3 and PAR, it was demonstrated that the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A is pathogenic according to ACMG guidelines.
