Neurogenetics Lecture Flashcards
Duchenne Muscular Dsytrophy - Overview
X-linked recessive
Incidence in males: 1/3000
Delay in motor development Onset of weakness ~ 3-4 years - pelvic and shoulder girdles Wheelchair bound by 10-12 years Death from involvement of respiratory and cardiac muscles in 20s
Characteristic posture in DMD
Stomach pushed out shoulders and legs back
What is deficient in DMD?
Dystrophin
Diagnosis of DMD (6)
Developmental delay in boys Muscle weaknes Raised CK EMG Muscle biopsy Molecular genetic testing - screen for deletions
What two signs show muscle weakness in DMD?
Gower’s sign
Toe walking
Carrier testing in DMD
Mutation testing identify mutation in affected boy test for mutation in female relatives wishing to know carrier status female carriers of known dystrophin mutations can be offered prenatal testing
When is onset usually in Huntington’s?
Between 30-50yrs
What type of genetic trait is Huntington’s?
Autosomal dominant
Early clinical signs of Huntington’s (9)
Clumsiness Agitation Irritability Apathy Anxiety Disinhibition Delusions Hallucinations Abnormal eye movements Depression
Later clinical signs of Huntington’s (10)
Dystonia Involuntary movements Trouble with balance and walking Trouble with activities that require manual dexterity Slow voluntary movements Difficulty initiating movement Inability to control speed and force of movement Weight loss Speech difficulties Stubbornness
Late clinical signs of Huntington’s (8)
Rigidity Bradykinesia (difficulty initiating and continuing movements) Severe chorea (less common) Serious weight loss Inability to walk Inability to speak Swallowing problems, danger of choking Inability to care for oneself
Pathology of Alzheimer’s (3)
Loss of cortical neurones Neurofibrillary tangles (intracellular) Senile plaques (extracellular)
What are senile plaques and what protein do they contain?
Extra cellular protein deposits containing amyloid Beta protein
What is the genetic aetiology of Alzheimers
an autosomal dominant trait in 5-10% of cases
(early onset)
Down syndrome (trisomy 21) (onset in 3rd or 4th decade)
Autosomal dominant Alzheimers disease - mutations
APP mutations (chromosome 21) Presenilin 1 (chromosome 14) Presenilin 2 (chromosome 1)
