Pedigrees and magnetic resonance imaging (MRI) studies of families with primary hypomagnesemia.

<p>(A) Pedigrees of families F1–F5. Filled symbols represent affected individuals, mutant alleles are indicated by a minus (−) and plus (+) sign, respectively. (B) Localization of the mutations in the CNNM2 protein structure (Uniprot Q9H8M5). CNNM2 contains a long signal peptide (64 amino acids) that is cleaved at the membrane of the endoplasmic reticulum. The remaining part of the CNNM2 protein is trafficked to the plasma membrane, where it becomes functionally active. White dots show the locations of the mutations. (C–D) MRI of the brain of patient F1.1 (C, T2 weighed images) and patient F2.1 (D, T2 weighed images). Left: Coronal images demonstrating a defect in myelinization of U-fibers (arrows) in patient F1.1 in contrast to a normal myelin pattern in patient F2.1. Center: Coronal T2 weighted images showing widened outer cerebrospinal liquor spaces (dashed arrows) and lack of opercularization (solid arrows) in patient F1.1, whereas a regular brain volume and insular lobe is observed in patient F2.1. Right: Absence of cerebellar structural abnormalities in patients F1.1 and F2.1 on axial T2 weighted images at the level of the trigeminal nerve.