Neurogenetics

Question 1

What is the inheritance of Duchenne Muscular dystrophy?

Answer 1

X linked receptive = dystrophin deficiency causes delay in motor development

Question 2

What is the progression of Duchenne Muscular dystrophy?

Answer 2

Onset of weakness at age 3-4 = pelvic/shoulder girdle
Wheelchair bound by age 10-12
Death by 20s due to involvement of cardiac and respiratory muscles

Question 3

What mutations are implicated in Duchenne Muscular dystrophy?

Answer 3

Large scale deletion in dystrophin in 70%
Point deletion and small insertions/deletions in 30%
1/3 of cases caused by novel mutation

Question 4

What are some signs of Duchenne Muscular dystrophy?

Answer 4

Calf hypertrophy, Gower’s sign and tiptoe walking

Question 5

How is Duchenne Muscular dystrophy?

Answer 5

Raised serum CK, EMG, muscle biopsy, molecular gene testing

Question 6

Who is offered testing for Duchenne Muscular dystrophy?

Answer 6

Female carriers of known dystrophin mutations

Question 7

What is the inheritance of Huntington’s disease?

Answer 7

Autosomal recessive = incidence is 1 in 20000, variable age dependent penetrance, molecular defect in HD

Question 8

What are the features of Huntington’s disease?

Answer 8

Onset between age 30-50 = involuntary movements and dementia with progression to severe dependency and death over 15-20 years

Question 9

What are the early clinical signs of Huntington’s disease?

Answer 9

Clumsiness, agitation, irritability, apathy, anxiety, disinhibition, delusions, abnormal eye movements, depression

Question 10

What are the late clincal signs of Huntington’s disease?

Answer 10

Dystonia, involuntary movements, trouble with balance/walking, trouble with manual dexterity, slow voluntary movements, weight loss, speech difficulties, inability to control speed/force of movement, rigidity, bradykinesis, severe chorea, swallowing problems

Question 11

What testing is offered for Huntington’s disease?

Answer 11

Prenatal and pregestational

Question 12

What causes spinal muscular atrophy?

Answer 12

Progressive loss of anterior horn cells in spinal cord and brainstem nuclei

Question 13

What is the inheritance of spinal muscular atrophy?

Answer 13

Autosomal recessive = caused by SMN1 deficiency, exon 7 is spliced out

Question 14

What are the features of spinal muscular atrophy?

Answer 14

Hypotonia, proximal muscle weakness and tongue fasciculation = variable age of onset and rate of progression

Question 15

How can the SMN1 deficiency that occurs in spinal muscular atrophy be corrected?

Answer 15

By altering the splicing of SMN2 mRNA

Question 16

What is the epidemiology of Alzheimer’s disease?

Answer 16

Responsible for 50-70% of dementia cases

Usually occurs in old age = 1/5 of people >80 affected

Question 17

What causes Alzheimer’s disease?

Answer 17

Loss of cortical neurons

Question 18

What are some features of Alzheimer’s disease?

Answer 18

Neurofibrillary tangles intracellularly, senile plaques extracellularly

Question 19

What are senile plaques?

Answer 19

Extracellular protein deposits containing amyloid beta protein (fragment of product of APP gene)

Question 20

What genes are implicated in Alzheimer’s disease?

Answer 20

APP and presenilin 1 and 2 = autosomal dominant mutations, occurs in 5-10%, early onset of disease

Question 21

What allele is associated with Alzheimer’s disease?

Answer 21

e4 allele = has some clustering in families

Question 22

What is the inheritance of multiple sclerosis?

Answer 22

Multifactorial and may cluster in families

More common in people with certain MHC haplotypes