Familial Brain Calcifications With Leukoencephalopathy: A Novel Variant.

Objective: To describe a family with primary familial brain calcifications (PFBCs) and leukoencephalopathy associated with a novel variant in .

Methods: We present 3 generations of a family with PFBC associated with a previously unreported variant in .

Results: A 24-year-old woman with migraine, bipolar disorder, and functional neurologic disorder was found to have bilateral calcifications of the basal ganglia and frontally predominant periventricular white matter disease. Her father had mild cognitive impairment and action tremor of the hands with basal ganglia and cerebellar calcifications found incidentally on head CT. Her paternal grandmother had severe parkinsonism and dementia with calcifications of the basal ganglia and cerebellum and diffuse, confluent periventricular white matter disease. Genetic testing in both the proband and her father revealed a variant (NM_002608.3:c.298C>T:p.Arg100Cys) not reported in publicly available databases. Multiple in silico analysis tools support pathogenicity.

Discussion: Our report identifies a novel variant associated with PFBC and highlights the rare association of leukoencephalopathy with -associated PFBC.