genetics in medicine II

Question 1

what is the epidemiology of CF?

Answer 1

commonest AR disorder inherited in Northern European Caucasian - carrier risk of 1 in 25 and incidence of 1 in 2500

Question 2

what is the basis of CF?

Answer 2

membrane transporter defect - defected salt transport across membrane resulting in thicker gland secretion, a build up of thick sticky mucus and effects to lungs. pancreas and GIT

Question 3

what are the clinical manifestations in the lungs?

Answer 3

thick bronchial mucus, progressive lung damage, recurrent chest infections and bronchiecstasis

Question 4

what are persistent lung pathogens?

Answer 4

aspergillus fumigatus, pseudomonas aeruginosa, mycobacterium abscessus and burkholderia cepacia complex

Question 5

what are the clinical manifestations in the pancreas?

Answer 5

inability to secrete digestive enzymes, growth failure and malabsorption

Question 6

why are men nearly always infertile?

Answer 6

absence or atrophy of the vas deferens

Question 7

what is the treatment?

Answer 7

daily physiotherapy, antibiotics and dietary supplements

Question 8

why may newborns need a bowel operation?

Answer 8

in 10% of newborns with CF - meconium ileus - obstruction due to impaction of viscid gut content

Question 9

how would you test?

Answer 9

sweat test - elevated Cl
molecular genetics
blood immunoreactive trypsin elevation

Question 10

what is CFTR?

Answer 10

cystic fibrosis transmembrane conductance receptor located at 7q31

Question 11

activation of CFTR causes what?

Answer 11

opening of the chloride channel and closure of the sodium channel - movement of water for mucus transport

Question 12

what is the chance of baby having CF?

Answer 12

husband chance of carrier x individuals chance x inheritance chance = 1/2 x 1/2 x 1/4 = 1/16

Question 13

what is heterozygous compound?

Answer 13

possessing two alleles at different gene loci that together will make the disease

Question 14

what is the most common CF mutation?

Answer 14

p.Phe508del - deletion of phenylanaline at position 508 of protein sequence for CFTR channel

Question 15

how would you do carrier testing for CF?

Answer 15

hard if do not know what you are looking for but if you do then - amplification using PCR, then OLA which will attach to the mutation site if present at 3’ end

Question 16

what is the epidemiology of HDD?

Answer 16

it affects 1 in 10-20,000 people of European ancestry

Question 17

what is the presentation of HDD?

Answer 17

middle age onset of 35-55 years - three main areas:
physical - chorea, weight loss and coordination and balance
cognitive - confusion, concentration and memory issues, poor executive functions, emotional blunting
mood - depression, apathy, irritability, obsessions, psychosis, agitation

Question 18

what is the genetic basis of HDD?

Answer 18

gene responsible will contain a CAG repeat expansion at the 5’ end - 11-34 is normal, over 40 is HDD
anticipation as is transmitted

Question 19

how does the repeat cause the presentation?

Answer 19

over 40 repeats / polyglutamines causes protein to aggregate in brain cells and therefore progressive death

Question 20

how would you detect HDD?

Answer 20

PCR to amplify region with repeats, gel and electric field to determine size, fluorescently label the probe, use ethidium bromide to detect

Question 21

why would you test?

Answer 21

removes uncertainty
relief
can make plans about pregnancy and family

Question 22

why would you not test?

Answer 22

removes hope
mental health
survivor guilt
damage to people around them

Question 23

in DNA mutation what does > mean?

Answer 23

change to

Question 24

in nomenclature what does x_ydel mean?

Answer 24

there has been a deletion from x to y inclusive

Question 25

what is EMARDD?

Answer 25

early onset myopathy, areflexia, respiratory distress and dysphagia

Question 26

what is the presentation of EMARDD?

Answer 26

congenital myopathy with proximal and generalised muscle weakness with respiratory difficulties, joint contracture and scoliosis. There is variable presentation with cleft palate and feeding difficulties.

Question 27

where is the MEGF10 gene located and what does it do?

Answer 27

it is associated with EMARDD and schizophrenia - 5q23.2