Genetics Flashcards
3 major patterns of inheritance
autosomal dominant
autosomal recessive
X linked
If someone has an AD gene, what chance does the child have of inheriting?
50%
What inheritance is hereditary haemochromatosis
AR
When both parents are carriers of AR genes, what chance does the child have of being affected and being a carrier?
25% affected
50% carrier
Who does X linked inheritance most commonly affect
Males
Why can X linked inheritance not pass from father to son?
an affected father only passes on a Y chromosome to his sons
Explanations of X linked inheritanc
No male to male tranmission (father passes Y chromosome only to his sons)
Daughters of an affected male are obligate carriers (an affected father passes his X chromosomes to all of his daughters)
Sons of a female carrier have a 50% chance of being affected and daughters have 50% chance of being carriers
What are haemophilias
Inherited clotting disorders which vary in severity according to the relative deficiency of the clotting factor concerned
Cause of haemophilia A
Reduced synthesis of Factor VIII
Cause of haemophilia B
Deficiency of Factor IX
Inheritance of haemophilias
X linked (recessive)
Generally affecting males born to female carriers
Some women who carry the haemophilia gene may have what?
Prolongation of APTT
Where can acquired haemophilia be seen?
Systemic inflammatory conditions such as RA because of the anti-factor VIII antibodies
How much of haemophilias are not familial i.e. sporadic?
30%
Differentials of haemophilia
DIC
Vit K deficiency
Disorders of fibrinogen or fibrinolytic production
Platelet disorders
Von Willebrands disease
Coag of haemophilias
Prolonged APTT
Normal PT and VWF
Treatment of haemophilia
Factor VIII/IX concentrate infusion
Acquired Factor VIII defieincy in mild cases - desmopressin or factor VIII in severe bleeding
Synthetic vasopressin
Fibrinolytic inhibitors
Vaccination against Hep B
Inheritance of familial hypercholesteraemia
AD
What criteria is used to aid diagnosis of familial hypercholesteraemia
Simon Boome criteria
Features of primary hypertriglyceraemia (without hypercholesteraemia)
Elevated very low density lipoprotein (Which confers even greater risk than LDL)
Present in childhood with eruptive xanthomas , lipaemia retinalis, retinal vein thrombosis, pancreatitis and hepatosplenomegaly
What can be detected in fasting plasma with primary hypertriglycaemia without hypercholestermaemia
Chylomicrons
Feautures of primary mixed (or combined) hyperlipidaemia
Elevated cholesterol and triglycerides
There is premature atherosclerosis
Assosiated with apoprotein E2 (high CV risk)
Remnant hyperlipidaemia is a rare cause - palmar xanthomas and tuberous xathomas over knees and elbows is characteristic
Diagnosis of FH
Lipid profile (two measurements)
Signs such as tendon xanthomata
Exclude secondary causes
What DNA evidence could prove FH
LDL receptor mutation
Familial defective apolipoprotein B100
PCSK9 mutation
