genetic disorders

Question 1

what are the symptoms of Huntington’s disease and in what age period does it come on?

Answer 1

Progressive chorea, dementia and psychiatric symptoms

30-50 years of age

Question 2

describe the genetics of Huntington’s disease

Answer 2

Autosomal dominant with genetic amplification
Due to a mutation in gene lenght - get repeats of CAG within the codon for HTT gene. Where there are 35 or less of these repeats you see no effect but as soon as it surpasses this symptoms of the condition develop - shows incomplete penetrance.
Repeats are prone to expansion particularly during meiosis in the father (if inherited through the father)
The expansion of the codon (which encodes a polyglutamine tract causes insoluble protein aggregates and neurotoxicity.

Question 3

what are the symptoms of myotonic dystrophy

Answer 3

progressive muscle weakness in early adulthood

• Also get myotonia and cataracts

Question 4

Describe the genetics of myotonic dystrophy

Answer 4

Autosomal dominant with genetic anticipation. Unstable length mutation of a CTG repeat in the 3’. This area of the gene is untranslated. When there are 50 or more repeats one of the protein binding factors needed for splicing binds to the long 3’ region, and is no longer available for splicing, thus disrupting splicing mechanism for other genes. Results in production of abnormal proteins.
Affects the CFTR channel and a chloride ion channel - myotonia

Question 5

Transmission by which sex results in a greater increase in repeats in myotonic dystrophy

Answer 5

females

Question 6

what is the pattern of inheritance in CF

what are the effects of CF/symptoms?

Answer 6

autosomal recessive.

Mucous filled lungs, recurrent respiratory infections and exocrine pancreatic insufficiency

Question 7

what is the most common mutation in CF?

Answer 7

phenylalanine deletion which prevents the normal folding of the protein and its insertion into the membrane

Question 8

how is muscular dystrophy inherited ?

Answer 8

X-linked recessive (knight’s move pattern)

Question 9

Which gene is involved in muscular dystrophy

Answer 9

DMD - codes for dystrophin which is involved in anchoring the cytoskeleton of each cell to the underlying basal lamina

Question 10

which biochemical test is used as a marker of muscular dystrophy

Answer 10

Serum creatinine kinase

Question 11

What is the mutation in BMD and how does it present

Answer 11

Becker’s muscular dystrophy
In-reading frame mutation. Less severe form of dystrophy. Have an older age of onset with wheelchair use occurring at a later age or not at all.

Question 12

what is the mutation in DMD and how will it present

Answer 12

Duchenne’s muscular dystrophy
Out of reading frame mutation. Results in no translation of the protein. Severe dystrophy with onset at ~3 years and wheelchair use at around 12 years of age

Question 13

Describe fragile X syndrome

Answer 13

Most common inherited cause of significant learning disability.
X-linked recessive condition with genetic anticipation. .
If a person has the full phenotype (>200 repeats) then the phenotype can be severe

Question 14

Give a short description of Down’s Syndrome

Answer 14

• recurrence risk depends on the cause
o trisomy 21 – for young parents, low risk at birth of 1/100
o translocation: may be high
• have learning difficulties
o most will walk and talk with some able to read and write
• heart malformation in >40%
• hypothyroidism in 30%

Question 15

Give a short description of Edward’s Syndrome

Answer 15

• trisomy 18 (bigger than chromosome 21)
• small chin
• clenched hands with overlapping fingers
• malformation of heart, kidneys and other organs
• if survive first year, generally have more profound learning difficulties

Question 16

Give a short description of Patau Syndrome

Answer 16

• trisomy 13
• congenital heart disease is usual
• about 50% die within one month
• like in Edward syndrome, approximately only 10% survive the first year, generally with profound learning difficulties
• cleft lip and palate
• microphthalmia – eyes too small
• abnormal ears
• clenched fists
• post-axial polydactyly (extra little finger)

Question 17

how do trisomies normally arise ?

Answer 17

Trisomies usually arise from maternal non-disjunction (failure of normal separation of the two chromosomes number 21, 18 or 13 during meiosis. These trisomies are more frequent with increased maternal age.

Question 18

what diseases are screened for using a Guthrie card ?

Answer 18

	For example: by mass spectrometry 
•	PKU
•	MCADD
	Immuno-assay: congenital hypothyroidism 
•	Cystic fibrosis 
	By HPLC
•	Sickle cell disorder