A novel gain-of-function mutation (W818R) of calcium-sensing receptor in a family with autosomal dominant hypocalcemia type 1

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A novel gain-of-function variant, W818R, in the CASR gene was identified in a family with autosomal dominant hypocalcemia type 1.
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The proband experienced recurrent seizures for decades, misdiagnosed as epilepsy, highlighting the importance of accurate genetic diagnosis.
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Whole-exome sequencing revealed the previously unreported CASR mutation, c.2452T>C (p.Trp818Arg), linked to the family's symptoms.
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Functional analyses confirmed that the W818R variant activates the MAPK signaling pathway, contributing to the disease's pathology.
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Treatment for symptomatic patients includes calcium supplementation and calcitriol to manage serum calcium levels and alleviate symptoms.

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