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

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.

SUBMITTER: Fan L

PROVIDER: S-EPMC8791931 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Fan Luoming L Miura Shiroh S Shimojo Tomofumi T Sugino Hirotoshi H Fujioka Ryuta R Shibata Hiroki H

Human genome variation 20220127 1

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 translatio ...[more]

PMID: 35082294

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Project description:UnlabelledMultiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein'menin' involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease.Learning pointsIdentification of a novel pathogenic MEN1 deletion mutation.MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology.Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome.

Dataset Information

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

Publications

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

Similar Datasets

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