5 research outputs found
A Novel PSEN1 Mutation in a Patient with Sporadic Early-Onset Alzheimer's Disease and Prominent Cerebellar Ataxia.
PSEN1 gene mutations represent the first cause of familiar early-onset Alzheimer's disease (EOAD). More than 190 mutations in PSEN1 have been reported to date. The clinical phenotype is mainly characterized by cognitive decline but movement disorders have been rarely described. We report a novel PSEN1 mutation (p.Thr147Pro) responsible for a sporadic early-onset dementia with prominent cerebellar symptoms, resembling a spinocerebellar syndrome. Neuroradiological and cerebrospinal fluid biomarkers examinations were performed on the patient, showing typical findings of EOAD and suggesting the pathogenicity of the novel mutation. Our study widens the number of unusual phenotypes related to PSEN1 mutations
Posterior cortical atrophy with prominent alexia without agraphia in a Tourette syndrome.
We report for the first time a patient with childhood-onset Tourette's syndrome (TS) who developed alexia without agraphia, acalculia, visual agnosia for objects and faces, and preserved mnesic functions in older age. Neuroimaging studies demonstrated temporo-parieto-occipital cortical atrophy and fronto-temporo-parieto-occipital hypometabolism, both more prominent on the left side. This case fulfils the diagnostic criteria of posterior cortical atrophy (PCA). The possible link between TS and PCA is discussed
Mutation in the SYNJ1Gene Associated with Autosomal Recessive, Early-Onset Parkinsonism
Autosomal recessive, early-onset Parkinsonism is clinically and genetically
heterogeneous. Here, we report the identification, by homozygosity mapping and
exome sequencing, of a SYNJ1 homozygous mutation (p.Arg258Gln) segregating with
disease in an Italian consanguineous family with Parkinsonism, dystonia, and
cognitive deterioration. Response to levodopa was poor, and limited by side
effects. Neuroimaging revealed brain atrophy, nigrostriatal dopaminergic defects,
and cerebral hypometabolism. SYNJ1 encodes synaptojanin 1, a phosphoinositide
phosphatase protein with essential roles in the postendocytic recycling of
synaptic vesicles. The mutation is absent in variation databases and in
ethnically matched controls, is damaging according to all prediction programs,
and replaces an amino acid that is extremely conserved in the synaptojanin 1
homologues and in SAC1-like domains of other proteins. Sequencing the SYNJ1 ORF
in unrelated patients revealed another heterozygous mutation (p.Ser1422Arg),
predicted as damaging, in a patient who also carries a heterozygous PINK1
truncating mutation. The SYNJ1 gene is a compelling candidate for Parkinsonism;
mutations in the functionally linked protein auxilin cause a similar early-onset
phenotype, and other findings implicate endosomal dysfunctions in the
pathogenesis. Our data delineate a novel form of human Mendelian Parkinsonism,
and provide further evidence for abnormal synaptic vesicle recycling as a central
theme in the pathogenesis