Genetics Flashcards
what is the genetic pattern in Duchenne Muscular Dystrophy
X-linked recessive
do all cases of DMD arise from the boys mother being.a carrier
no, 1/3 cases arise from a spontaneous mutation occurring
when do symptoms of DMD begin
aged 3-4, picked up when boys are not hitting milestones
list the approximate age when boys with DMD will be wheelchair bound and then when they will die
wheelchair bound - 10/12
death - 20s due to respiratory muscles failing leading to cardiorespiratory arrest
DMD occurs when there is a mutation in which gene
dystrophin gene
what is the function of the dystrophin gene
aids actin and myosin contraction, without it will result in progressive loss of muscle cells and wastage
when looking at cells histologically where does dystrophin appear in the cell normally
around the outside in the cell membrane - with DMD it is no longer present
what are the 2 types of dystrophin mutations that can occur
large scale deletions of the dystrophin gene (70% of cases)
smaller, point mutations (30% of cases)
how does DMD present
developmental delay especially gross motor but can be global
weakness in the pelvic girdle muscles
Gowers sign +ve
exaggerated lumbar lordosis
contractures of the Achilles tendon making walking difficult
what is Gowers sign
when asking child to stand up from sitting on the ground they will use their hands to aid them standing up as pelvic girdle muscles are weakened
what tests are used to diagnose DMD
raised serum creatine levels - not diagnostic but shows muscle pathology
molecular genetic screening
electromyography
muscle biopsy
what is Huntingtons Disease
a progressive neurodegenerative disease of autosomal dominant inheritance
when are symptoms likely to begin in HD
age 30-50 but can vary
from symptom onset, how long do patients usually live with HD
15-20 years but progress to severe dependancy before this
list the clinical signs of HD
involuntary choreiform movements of head, limbs, trunk and face associated with dementia rigidity bradykinesia speech and swallowing impaired
what is caudate atrophy
loss of cells from basal ganglia, flattens normal convex curve of the lateral walls of the ventricles
describe the molecular genetic defect in HD
CAG repeat expansion
CAG codes for glutamine and expansion results in production of abnormal protein with glutamine residues which is neurotoxic
the older a patient with genetic predisoposition the lower their risk of HD true/false
true
what is the inheritance pattern in spinal muscular atrophy
autosomal recessive
in spinal muscular atrophy what gene is affected
SMN1 gene which codes for a specific exon essential for preventing motor neuron loss
describe the clinical presentation of spinal muscular atrophy
hypotonia
muscle weakness
wasting of proximal skeletal muscles
all due to loss of anterior horn cells
what is the treatment for spinal muscular atrophy
synthetic oligonucleotide injection which splices exon 7 into identical gene SMN2 - treatment only prevents progression does not reverse condition
Alzheimers is the most common cause of what disease
dementia
describe the pathophysiology of Alzheimers
loss of cortical neurons, neurofibrillary tangles with senile plaques
senile plaques contain what protein
amyloid B protein which is a fragment product of APP - amyloid precursor protein found on chromosome 21
what condition is associated with an increased risk of developing Alzheimers at a younger age
Downs Syndrome
the rarer autosomal dominant forms of Alzheimers have an earlier or later onset
earlier onset
