Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

ABSTRACT: Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-jun

SUBMITTER: Schottlaender LV 

PROVIDER: S-EPMC7058839 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature