Sat-072 a Novel Mutation in the Cnnm2 Gene Causing Hypomagnesaemia And neurological Impairment In an adolescent

Case Report: CNNM2 Mutations Cause Damaged Brain Development and Intractable Epilepsy in a Patient Without Hypomagnesemia

“…Our patient showed a mild intellectual disability, with a de novo heterozygous missense CNNM2 variant. Reviewing the literature (Stuiver et al, 2011;Arjona et al, 2014;Accogli et al, 2019;Bamhraz et al, 2020;Franken et al, 2021), we found that severe intellectual disability all occurred in patients with homozygous missense variants. Hence, it can be speculated that homozygous variants significantly affect the function of CNNM2, leading to severe phenotypes.…”

“…And all four patients showed hypomagnesemia with a renal defect in Mg 2+ reabsorption. The other two homozygous variants (c.364G>A, p.Glu122Lys; c.1642G>A, p.Val548Met) (Arjona et al, 2014 ; Accogli et al, 2019 ) and 13 heterozygous in CNNM2 occurred in unrelated families (Kosmicki et al, 2017 ; Snoeijen-Schouwenaars et al, 2019 ; Bamhraz et al, 2020 ; Franken et al, 2021 ). In 24 cases, different variant domains were listed in Figure 1E .…”

“…Heterozygous variants in CNNM2 gene were described for the first time in two unrelated families with autosomal dominant renal hypomagnesemia, displaying severely lowered serum Mg 2+ levels and a defect in tubular Mg 2+ reabsorption, without other electrolyte disturbances or neurological function impairment (Stuiver et al, 2011 ). Subsequently, the other four heterozygous and two homozygous variants in CNNM2 gene were reported to cause patients variable degrees of intellectual disability except for autosomal dominant or recessive renal hypomagnesemia, and most of whom had seizures(Arjona et al, 2014 ; Accogli et al, 2019 ; Bamhraz et al, 2020 ). What is noteworthy is that all reported cases showed the varying degrees of hypomagnesemia up to now, with or without neurological impairment.…”