TY - JOUR
T1 - A novel 1-bp deletion variant in DAG1 in Japanese familial asymptomatic hyper-CK-emia
AU - Fan, Luoming
AU - Miura, Shiroh
AU - Shimojo, Tomofumi
AU - Sugino, Hirotoshi
AU - Fujioka, Ryuta
AU - Shibata, Hiroki
N1 - Funding Information:
We are grateful to the family for allowing us to report their cases. Written informed consent was obtained from all participating individuals. This study was approved by the Ethics Committees of Kurume University School of Medicine (#79) and of Kyushu University, Faculty of Medicine (#397-01). This work was supported by the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Asymptomatic hyper-CK-emia (ASCK) is characterized by persistent elevation of creatine kinase (CK) in serum without any neurological symptoms. We ascertained a two-generation family of ASCK patients without clear neurological abnormalities except for the high levels of serum CK (810.5 ± 522.4 U/L). We identified a novel 1-bp deletion variant in the DAG1 gene shared by the patients in the family (NM_001177639: exon 3: c.930delC:p.R311Gfs*70). The variant causes premature termination of translation at codon 477, resulting in a protein product completely devoid of the essential DAG1 domain. Since ASCK has been associated with DAG1 in only one case carrying compound heterozygous missense variants, our new finding of a novel 1-bp deletion revealed the previously unknown dominant effect of DAG1 on ASCK.
AB - Asymptomatic hyper-CK-emia (ASCK) is characterized by persistent elevation of creatine kinase (CK) in serum without any neurological symptoms. We ascertained a two-generation family of ASCK patients without clear neurological abnormalities except for the high levels of serum CK (810.5 ± 522.4 U/L). We identified a novel 1-bp deletion variant in the DAG1 gene shared by the patients in the family (NM_001177639: exon 3: c.930delC:p.R311Gfs*70). The variant causes premature termination of translation at codon 477, resulting in a protein product completely devoid of the essential DAG1 domain. Since ASCK has been associated with DAG1 in only one case carrying compound heterozygous missense variants, our new finding of a novel 1-bp deletion revealed the previously unknown dominant effect of DAG1 on ASCK.
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U2 - 10.1038/s41439-022-00182-0
DO - 10.1038/s41439-022-00182-0
M3 - Article
AN - SCOPUS:85123757600
SN - 2054-345X
VL - 9
JO - Human Genome Variation
JF - Human Genome Variation
IS - 1
M1 - 4
ER -