Key result
De novo CNNM2 pathogenic variant linked to pediatric hypomagnesemia, seizures, and mental retardation.
Why the study?
The genetic etiology of Hypomagnesemia, epilepsy, and mental retardation syndrome (HSMR) in affected children was explored to identify causative variants.
Case Report (n=1)
No
A de novo heterozygous c.1448delT variant in the CNNM2 gene was identified as the probable cause of Hypomagnesemia, epilepsy, and mental retardation syndrome in a child.
Answers are grounded in this paper and cite their sources.
Supports CNNM2 testing in refractory pediatric hypomagnesemia with seizures; extends mutational spectrum but remains hypothesis-generating pending replication.
OBJECTIVE: To explore the genetic etiology of a child with Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR). METHODS: A child who was admitted to the Children's Hospital of Shandong University on July 9, 2021 due to repeated convulsions for 2 months was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-and-7-month-old male, had presented with epilepsy and global developmental delay. Serological testing revealed that he has low serum magnesium. Genetic testing showed that the child has harbored a heterozygous c.1448delT (p.Val483GlyfsTer29) variant of the CNNM2 gene, which was de novo in origin. The variant has caused substitution of the Valine at position 483 by Glycine and formation of a termination codon after 29 amino acids at downstream. As predicted by Swiss-Model online software, the variant may alter the protein structure, resulting in a truncation. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1448delT (p.Val483GlyfsTer29) was predicted as a pathogenic variant (PVS1+PS2+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.1448delT variant of the CNNM2 gene probably underlay the HSMR in this child. Above finding has enriched the phenotype-genotype spectrum of the CNNM2 gene.
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Wang et al. (2023) conducted a case report in Hypomagnesemia, epilepsy and mental retardation syndrome (HSMR) (n=1). CNNM2 gene variant (c.1448delT) was evaluated on Genetic etiology of HSMR. A de novo heterozygous c.1448delT (p.Val483GlyfsTer29) pathogenic variant in the CNNM2 gene was identified as the probable genetic etiology for a child with hypomagnesemia, seizures, and mental retardation.
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