Autosomal dominant striatal degeneration

Autosomal dominant striatal degeneration: Description, Causes and Risk Factors:Autosomal dominant striatal degeneration (ADSD) is an adult-onset movement disorder characterized by bradykinesia, dysarthria and muscle rigidity. To date, ADSD has been observed in seven individuals in one family.ADSD is characterized by dysfunction and changes of the striatal part of the basal ganglia, visible on MRI scans. It is caused by mutation in the PDE8B gene (5q13.3-q14.1) and is transmitted in an autosomal dominant manner with complete penetrance in the investigated family.The autosomal dominant striatal degeneration causing mutation results in a loss of all three functional domains of PDE8B, which most likely causes a complete loss of function of the truncated protein. To prove the loss of phosphodiesterase enzymatic activity of mutated PDE8B, researchers transfected COS-7 cells with isoform 1 of wild-type PDE8B (pEGFP-PDE8BWt), mutated PDE8B (pEGFP-PDE8B-Mut), or empty vector (pEGFP). COS-7 cells were cultivated in Dulbecco's modified Eagle's medium high glucose with L-Glutamine and with sodium pyruvate (Th. Geyer) supplemented with 5% fetal calf serum (invitrogen) and 1% Pen/Strep-Premix (Carl-Roth) at 37°C with 5% CO2. Transfections were performed with either TurboFect (Fermentas) or Nanofect (PAA Laboratories) according to the manufacturers' recommendations. A full open reading frame clone containing wild-type PDE8B isoform 1 was obtained from Imagenes. The ADSD-causing mutation (c.94G>C+c.95delT) was introduced with the QuickChange XL Site-Directed Mutagenesis Kit (Stratagene). Wild-type and mutant PDE8B were PCR amplified via primers containing HindIII and EcoR1 sites. The PCR products were subcloned into pEGFP-N3 (Clontech) to generate constructs expressing PDE8B C-terminally fused to enhanced green fluorescent protein (EGFP). The inserts of all constructs were verified by DNA sequencing.Elucidating the causative genetic defects of monogenic forms of common polygenic diseases and related disorders has contributed eminently to understanding the pathomechanisms underlying Parkinson disease and other related neurological disorders. Researchers believe that the functional analysis of PDE8B will help to elucidate the pathomechanism of ADSD and will contribute to our understanding of other related neurological disorders.We believe that the functional analysis of PDE8B will help to further elucidate the pathomechanism of ADSD as well as contribute to a better understanding of movement disorders.Autosomal dominant striatal degenerationSymptoms:Onset of symptoms of autosomal dominant striatal degeneration  is in the fourth to fifth decade of life with mild progressive dysarthria and hypokinesia. Mild bradykinesia presents predominantly as gait disturbance but also as a general slowing of movement. Dysdiadochokinesia is also present and muscle tone is slightly increased. Additional features include stiffness of the tongue and, in some patients, mild difficulties in swallowing.Diagnosis:Diagnosis is based on brain MRI which shows distinctive and characteristic symmetric lesions of the striatum that appear earlier than the onset of symptoms. A good correlation has been observed between clinical signs and the degree of MRI abnormalities. Differential diagnoses include other degenerative diseases causing hypokinesia (diminished or slow movement). However, unlike for these diseases, in ADSD, tremor is not observed. Differential diagnoses also include neuroferritinopathy. However, autosomal dominant striatal degeneration is characterized by hypokinesia whereas neuroferritinopathy is characterized by hyperkinesia. The characteristic MRI changes of the striatum can be regarded as pathognomonic for ADSD. Antenatal diagnosis is currently not available but is probably not necessary because of the mild course of the disease.Treatment:There is currently no known treatment for ADSD and symptoms do not respond to treatment with levodopa. However, the course of the disease is mild and allows affected individuals to lead a virtually normal life. Life expectancy does not appear to be affected.NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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