Key result
Novel CNNM2 mutation expands the HSMR phenotype to include congenital heart disease.
Why the study?
Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease with only 24 cases reported and incomplete clinical characterization, complicating diagnosis.
Case Report (n=1)
The identification of a novel CNNM2 mutation (Tyr189Cys) in a 4-month-old patient expands the phenotypic spectrum of HSMR syndrome to include congenital heart disease.
Answers are grounded in this paper and cite their sources.
Suggests CNNM2 variants may associate with congenital heart disease in HSMR syndrome; extends phenotype but leaves open generalizability from one case.
BACKGROUND: Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging. METHODS: Trio-whole-exome sequencing was used for the patient and her parents, and the structure of the variant protein was analyzed by molecular dynamics. Finally, the characteristics of HSMR were summarized by reviewing the previous literature. RESULTS: The main disease manifestations in the patient were seizures, liver function damage, hypomagnesemia, atrial septal defect, and sinus arrhythmia. A novel mutation in CNNM2 (c.566A>G/p.Tyr189Cys) was identified by genetic detection. The parents were wild type, and the mutation was rated as pathogenic by American College of Medical Genetics and Genomics guidelines. Ab initio modeling and molecular dynamics simulation show that the mutation destroys the surrounding hydrogen bonds, which may reduce the local stability of the protein structure. In the previous literature, only 24 children with HSMR have been reported, mainly manifested as hypomagnesemia, mental retardation, seizures, and language and motor impairment. CONCLUSION: We have reported the second case of HSMR in the Chinese population, which further expands the phenotypic spectrum of congenital heart disease and the variation spectrum of CNNM2.
No takes yet. Share an insight, caveat, or question.
Xu et al. (2022) conducted a case report in Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome (n=1). CNNM2 mutation (c.566A>G/p.Tyr189Cys) was evaluated on Genetic mutation identification and clinical manifestations. A novel pathogenic mutation in CNNM2 was identified in a 4-month-old patient with HSMR, expanding the phenotypic spectrum to include congenital heart disease.
Synapse has enriched 10 related papers. Consider them for comparative context: