Maxent Kraft Angelman syndrome GENOMIC IMPRINTING DISORDER OF THE - PowerPoint PPT Presentation

Maxent Kraft

Angelman syndrome GENOMIC IMPRINTING DISORDER OF THE BRAIN Presented by Sybille Kraft Bellamy

DNA DEOXYRIBONUCLEIC ACID Genetics are the study of heredity. How traits are passed from the generation to the next. 22 500 genes DNA is protected in the nucleus it is transcribed in RNA. RNA is translated in a sequence of amino acids . Amino acids are going to be linked together to form a protein. Shape = function

Karyotype

Angelman syndrome Pathophysiology/GENOTYPE Angelman syndrome is caused by the loss of the normal maternal contribution to a region of chromosome 15, most commonly by deletion of a segment of that chromosome. 15q11-13 Uni parental disomy Translocation Single gene mutation UBE3A GENE

DIFFERENTIATION GENE EXPRESSION METHYLATION In different cell types we have different DNA sequences turned on and off in a process called DIFFERENTIATION. We can control what genes are turned on and how much RNA have to be transcribed and that is called GENE EXPRESSION . Allele is silent or activated Methylation is a process in which methyl groups are added on to your DNA sequence = affect how the genes are transcribed. Off.

Genomic imprinting

Angelman syndrome Clinical features Phenotype Consistent (100 %)  Developmental delay - Functionally severe  Speech impairment minimal use of words  Movement balance disorder Ataxia (poor muscle movement coordination)  Behavioral uniqueness - smile laugher happy demeanor - hand flapping Frequent (80%)  Microcephaly (absolute relative)  Seizures onset before 3 years old  Abnormal EEG large amplitude slow spike waves Associated (20 80 %) Strabismus, swallowing disorder, failure to thrive, feeding disorder, sensitivity to heat, sleep disturbance, constipation, drooling fascination for water.

Ubiquitin protein ligase E3A UBE3A Specific gene in 15q11-q13 UBE3A Enzyme involved in targeting proteins for degradation within cells. Both copies of UBEA3A are active in body’s tissues. Only the maternal copy is active in brain neurons.

Angelman syndrome (AS) treatment There is currently no cure available. Epilepsy is controlled by the use of one or more types of anticonvulsant / AS is usually associated with having multiple varieties of seizures .VNS (Vagus Nerve Stimulation) Melatonin – average of 5 hours night Mild laxative - chronicle constipation Control for scoliosis osteoporosis OT PT ST ABA therapist , music…

LGIT Low Glycemic Index Treatment Therapeutical diet at this day is the only successful way to reduce the severity of seizures and other health problems.