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1.  A novel de novo pathogenic mutation in CACNA1A gene 
PMCID: PMC3477248  PMID: 23038654
episodic ataxia type 2; CACNA1A; p.R1346Stop; acetazolamide; cerebellar vermis
2.  SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia 
Neurogenetics  2013;15(1):23-30.
Idiopathic Basal Ganglia Calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and Taqman copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in 2 of the 27 cases of IBGC (7%). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. Taqman copy-number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256 bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early-onset dystonia in this family. The identification of a SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated.
PMCID: PMC3969760  PMID: 24135862
basal ganglia calcification; dystonia; SLC20A2; THAP1; genomic deletion; mutation
3.  An adult-onset leukoencephalopathy with axonal spheroids and pigmented glia accompanied by brain calcifications 
Journal of neurology  2013;260(10):10.1007/s00415-013-7093-x.
PMCID: PMC3865925  PMID: 24036850
adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; CSF1R; calcification; computed tomography; white matter; differential diagnosis
4.  Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis 
Neurology  2013;80(19):1771-1777.
We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C>A) missense mutation.
Three patients with GRN A9D mutations were evaluated clinically and came to autopsy with subsequent neuropathologic examination.
The clinical diagnoses of patients with GRN A9D mutations were amyotrophic lateral sclerosis, atypical extrapyramidal disorder, and behavioral variant frontotemporal dementia. Immunohistochemistry for TAR DNA-binding protein 43 (TDP-43) revealed variability in morphology and distribution of pathology. One patient had notable involvement of motor neurons in the spinal cord as well as type B TDP-43, whereas 2 other patients had type A TDP-43.
The clinical presentation of the GRN A9D missense mutation is not restricted to behavioral variant frontotemporal dementia and may include aphasia, extrapyramidal features, and, notably, amyotrophic lateral sclerosis.
PMCID: PMC3719429  PMID: 23596077
5.  Mutations in the colony stimulating factor 1 receptor (CSF1R) cause hereditary diffuse leukoencephalopathy with spheroids 
Nature Genetics  2011;44(2):200-205.
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominantly inherited central nervous system white matter disease with variable clinical presentations including personality and behavioral changes, dementia, depression, parkinsonism, seizures, and others1,2. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor receptor 1 (encoded by CSF1R) in 14 families affected by HDLS. In one kindred, the de novo occurrence of the mutation was confirmed. Follow-up sequencing analyses identified an additional CSF1R mutation in a patient clinically diagnosed with corticobasal syndrome (CBS). In vitro, CSF-1 stimulation resulted in the rapid autophosphorylation of selected tyrosine-residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from a partial loss of CSF1R function. Since CSF1R is a critical mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.
PMCID: PMC3267847  PMID: 22197934
6.  Familial idiopathic basal ganglia calcification: a challenging clinical-pathological correlation 
Journal of neurology  2009;256(5):839-842.
PMCID: PMC2875477  PMID: 19252803
Fahr disease; brain calcinosis; idiopathic basal ganglia calcification

Results 1-6 (6)