A novel 1-bp deletion variant in DAG1 in Japanese familial asymptomatic hyper-CK-emia

Luoming Fan; Shiroh Miura; Tomofumi Shimojo; Hirotoshi Sugino; Ryuta Fujioka; Hiroki Shibata

doi:10.1038/s41439-022-00182-0

A novel 1-bp deletion variant in DAG1 in Japanese familial asymptomatic hyper-CK-emia

Hum Genome Var. 2022 Jan 27;9(1):4. doi: 10.1038/s41439-022-00182-0.

Authors

Luoming Fan¹, Shiroh Miura², Tomofumi Shimojo¹, Hirotoshi Sugino³, Ryuta Fujioka⁴, Hiroki Shibata¹

Affiliations

¹ Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
² Department of Neurology and Geriatric Medicine, Ehime University Graduate School of Medicine, Ehime, Japan. shiroh46@m.ehime-u.ac.jp.
³ Sugino Pediatric Clinic, Hiroshima, Japan.
⁴ Department of Food and Nutrition, Beppu University Junior College, Oita, Japan.

Abstract

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.