Case Report: Novel mutations in are associated with autosomal dominant tonic-clonic and myoclonic epilepsy and recessive Parkinsonism, psychosis, and intellectual disability.

F1000Res 2017 24;6:553. Epub 2017 Apr 24.

Center for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.

Mutations disrupting presynaptic protein TBC1D24 are associated with a variable neurological phenotype, including DOORS syndrome, myoclonic epilepsy, early-infantile epileptic encephalopathy, and non-syndromic hearing loss. In this report, we describe a family segregating autosomal dominant epilepsy, and a 37-year-old Caucasian female with a severe neurological phenotype including epilepsy, Parkinsonism, psychosis, visual and auditory hallucinations, gait ataxia and intellectual disability. Whole exome sequencing revealed two missense mutations in the gene segregating within this family (c.1078C>T; p.Arg360Cys and c.404C>T; p.Pro135Leu). The female proband who presents with a severe neurological phenotype carries both of these mutations in a compound heterozygous state. The p.Pro135Leu variant, however, is present in the proband's mother and sibling as well, and is consistent with an autosomal dominant pattern linked to tonic-clonic and myoclonic epilepsy. In conclusion, we describe a single family in which mutations cause expanded dominant and recessive phenotypes. In addition, we discuss and highlight that some variants in might cause a dominant susceptibility to epilepsy.

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http://dx.doi.org/10.12688/f1000research.10588.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473401PMC
April 2017
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