genetics in medicine II Flashcards
what is the epidemiology of CF?
commonest AR disorder inherited in Northern European Caucasian - carrier risk of 1 in 25 and incidence of 1 in 2500
what is the basis of CF?
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
what are the clinical manifestations in the lungs?
thick bronchial mucus, progressive lung damage, recurrent chest infections and bronchiecstasis
what are persistent lung pathogens?
aspergillus fumigatus, pseudomonas aeruginosa, mycobacterium abscessus and burkholderia cepacia complex
what are the clinical manifestations in the pancreas?
inability to secrete digestive enzymes, growth failure and malabsorption
why are men nearly always infertile?
absence or atrophy of the vas deferens
what is the treatment?
daily physiotherapy, antibiotics and dietary supplements
why may newborns need a bowel operation?
in 10% of newborns with CF - meconium ileus - obstruction due to impaction of viscid gut content
how would you test?
sweat test - elevated Cl
molecular genetics
blood immunoreactive trypsin elevation
what is CFTR?
cystic fibrosis transmembrane conductance receptor located at 7q31
activation of CFTR causes what?
opening of the chloride channel and closure of the sodium channel - movement of water for mucus transport
what is the chance of baby having CF?
husband chance of carrier x individuals chance x inheritance chance = 1/2 x 1/2 x 1/4 = 1/16
what is heterozygous compound?
possessing two alleles at different gene loci that together will make the disease
what is the most common CF mutation?
p.Phe508del - deletion of phenylanaline at position 508 of protein sequence for CFTR channel
how would you do carrier testing for CF?
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
what is the epidemiology of HDD?
it affects 1 in 10-20,000 people of European ancestry
what is the presentation of HDD?
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
what is the genetic basis of HDD?
gene responsible will contain a CAG repeat expansion at the 5’ end - 11-34 is normal, over 40 is HDD
anticipation as is transmitted
how does the repeat cause the presentation?
over 40 repeats / polyglutamines causes protein to aggregate in brain cells and therefore progressive death
how would you detect HDD?
PCR to amplify region with repeats, gel and electric field to determine size, fluorescently label the probe, use ethidium bromide to detect
why would you test?
removes uncertainty
relief
can make plans about pregnancy and family
why would you not test?
removes hope
mental health
survivor guilt
damage to people around them
in DNA mutation what does > mean?
change to
in nomenclature what does x_ydel mean?
there has been a deletion from x to y inclusive
what is EMARDD?
early onset myopathy, areflexia, respiratory distress and dysphagia
what is the presentation of EMARDD?
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.
where is the MEGF10 gene located and what does it do?
it is associated with EMARDD and schizophrenia - 5q23.2
