Week 108

Question 1

Huntington disease

Answer 1

Autosomal dominant

Neurodegenerative; causing lack of coordination, unsteady gain, problems with mood or cognition, chorea, early death (life expect around 15y after diagnosis)

Accumulation of mutant HUNTINGTIN protein

Question 2

Marfan syndrome

Answer 2

Autosomal dominant

Connective tissue disorder; unusually tall with long limbs and long thin fingers and toes; associated with heart valve and aorta defects leading to death.

Question 3

Familial hypercholestrolaemia

Answer 3

Autosomal dominant

High cholestrol levels, specifically LDL, leading to early CVD.

Question 4

Spinocerebellar ataxia

Answer 4

Autosomal dominant

Progressive degenrative disease causing slowly progressive incoordination of gain and associated poor coordination of hands, speech and eye movements.

Question 5

Familial adenomatous polyposis

Answer 5

Autosomal dominant

Hundreds or thousands of small polyps grow in the large bowel which will almost definitely develop into cancer. Needs regular colonoscopies and possible bowel resection.

Question 6

Hereditary breast and ovarian cancer

Answer 6

Autosomal dominant

HBOC syndrome is associated with young diagnoses of breast or ovarian cancer within the family. It is caused by BRCA1 and BRCA2 gene mutations.

Question 7

Myotonic dystrophy

Answer 7

Autosomal dominant

Muscular dystrophy (progressive muscle wasting and weakness) that starts in adulthood. Prolonged muscle contractions (myotonia) and not being able to relax certain muscles after use e.g. difficulty releasing grip.

Question 8

Long QT syndrome

Answer 8

Autosomal dominant

Delayed repolarisation of the heart increases risk of epiodes of TdP and episodes may lead to palpitations, fainting and sudden death due to VF. Implantable ICD.

Question 9

Cystic fibrosis

Answer 9

Autosomal recessive

Affects mostly lungs but also pancrease, liver, kidneys and intestine. Causes difficulty breathing and coughing up mucus resulting in frequent lung infections. Also sinus infections, poor growth, fatty stool, clubbing, infertility. Mutations in CFTR.

Question 10

Phenylketonuria

Answer 10

Autosomal recessive

Impaired metabolism of amino acid phenylalanine due to absence of phenylalanine hydroxylase (PAH). Protein rich foods or aspartame sweetener can poison sufferers. Phenylalanine build up affects brain development and function, and can lad to intellectual disability, seizures and other severe problems.

Question 11

Beta thallasemia

Answer 11

Autosomal recessive

Blood disorder that reduces haemoglobin production, leading to anaemia, hypoxaemia, weakness, fatigue, pallor, increased risk of clots and more serious complications. Children develop life threatening anaemia, often don’t gain weight and may develop jaundice.

Question 12

Sickle cell anaemia

Answer 12

Autosomal recessive

Abnormality in haemoglobin leads to RBCs assuming abnormal, rigid, sickle shape under certain circumstances. Associated with severe infections, attacks of severe pain (sickle cell crisis), stroke, and increased risk of death,

Question 13

Tay Sachs disease

Answer 13

Autosomal recessive

Progressive destruction of neurons in the brain and spinal cord. Becomes apparently in infancy (around 6 months), and infants lose motor skills such as turning over, sitting and crawling. They also have an exaggerated startle reaction to loud noises. They go on to experience seizures, vision and hearing loss, disability and paralysis. Usually children die in early childhood.

Question 14

Spinal muscular atrophy

Answer 14

Autosomal recessive

LOF of neuronal cells in anterior horn of spinal cord leading to system-wide muscle wasting. Often affects proximal muscles and lung muscles first, leading to areflexia, muscle weakness and poor muscle tone, limpness etc.

Question 15

Duchenne muscular dystrophy

Answer 15

X-linked recessive

Muscle degeneration and premature death due to mutation in dystrophin gene. Symptoms appear around 2y: progressive proximal muscle weakness of the legs and pelvis with loss of muscle mass, which spreads to arms, next and other areas.

Elevated CK levels.

Question 16

Haemophilia A

Answer 16

X-linked recessive

Deficiency in clotting factor VIII causes increased bleeding. Internal or external bleeding episodes (“bleeds”) e.g. haematomas, prolonged bleeding.

Question 17

RG colour blindness

Answer 17

X-linked recessive

Difficulty discriminating between red and green hues due to absence or mutation of red or green retinal photoreceptors.

Question 18

MYH associated polyposis

Answer 18

Autosomal recessive

Development of multiple adenomatous colon polyps with increased risk of colorectal cancer.

Question 19

Genomic imprinting

Answer 19

One gene copy is inherited form mother and one from father, and both copies are usually active. In imprinting, only one is expressed and the other is “imprinted”. If a faulty gene is imprinted this will not cause problems but if a healthy gene is imprinted and the remaining copy is faulty, this can cause disease.

Question 20

Uniparental disomy

Answer 20

Person receives two copies of a chromosome from one parent and no copies from the other parent.

Question 21

Beckwith-Wiedemann syndrome

Answer 21

Autosomal dominant

Paternal UPD of chromosome 11 means that offspring is missing some features of the gene that are only active on the maternal copy of the gene.

Overgrowth syndrome: affected infants are larger than normal (macrosomia) and taller than peers. By adulthood they are not unusually tall. Assymetric appearance (hemihyperplasmia). Increased risk of several types of cancers.

Question 22

Prader-Willi syndrome

Answer 22

autosomal dominant

Maternal UPD of chromosome 15 means that offspring is lacking the genes within chromosome 15 that are only active on the male copy of the gene.

Neonatal hypotonia, feeding difficulties and poor growth. Developmental delay, LD, insatiable appetite and obesity.

Question 23

Angelman syndrome

Answer 23

AUTOSOMAL DOMINANT

Paternal UPD of chromosome 15.

Affects nervous system: delayed development, intellectual disability, speech imparment, ataxia, recurrent seizures, small head size, happy excitable demeanor with frequent smiling, laughter and hand flapping movements, hyperactivity, short attention span, fascination with water.

Question 24

Mosaicism

Answer 24

Two or more DIFFERENT genetic or chromosomal cell lines within a single individual or tissue (somatic = not germ line cell; germ line = germ line cells).

Question 25

Mitochondrial inheritence

Answer 25

Mitochondria have their own set of DNA. Only MATERNAL mitochondria are passed on at fertilisation so mitochondrial genes are always inherited maternally. Includes LHON, MELAS, MERRF, Leigh sydnrome, MIDD.

Question 26

Leber’s hereditary optic neuropathy (LHON)

Answer 26

Mitochondrial disorder (mitochondrial inheritence)

Profound and gradual vision loss due to death of cells within the optic nerve. Often presents in teens and twenties and affects males more than females.

Question 27

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)

Answer 27

Mitochondrial disorder (mitochondrial inheritence)

(MELAS) is a condition that affects many of the body’s systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).
Most people with MELAS have a buildup of lactic acid in their bodies, a condition called lactic acidosis. Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. Less commonly, people with MELAS may experience involuntary muscle spasms (myoclonus), impaired muscle coordination (ataxia), hearing loss, heart and kidney problems, diabetes, and hormonal imbalances.

Question 28

Myoclonic epilepsy with ragged red fibres (MERRF)

Answer 28

Mitochondrial disorder (mitochondrial inheritence)

Muscle twitches (myoclonus), weakness (myopathy), progressive stiffness (spasticity). Muscle cells under microscopy are called ragged-red fibers.

Question 29

Leigh syndrome

Answer 29

Mitochondrial disorder (mitochondrial inheritence)

Severe neurological disorder arises in first year of life characterised by progressive loss of mental and movement abilities and results in death within a couple of years usually due to respiratory failure.

Question 30

Maternally inherited diabetes and deafness (MIDD)

Answer 30

Mitochondrial disorder (mitochondrial inheritence)

Non insulin dependent diabetes usually presents before age 40 due to defect in beta cell function. Sensorineural deafness develops in most diabetes sufferers; severity of deafness is variable but may require a hearing aid.

Question 31

Haemochromatosis

Answer 31

Autosomal recessive

Question 32

Adult polycystic kidneydisease

Answer 32

Autosomal dominant

Question 33

Neurofibromatosis

Answer 33

Cancer

Autosomal dominant

Question 34

Alzheimer’s

Answer 34

multifactorial

Question 35

Neural tube defects

Answer 35

multifactorial

Question 36

Fragile X syndrome

Answer 36

chromosomal

Question 37

Genetic test for HD?

Answer 37

Counting the number of CAG repeats: Below 28=N and above 40=increased HD risk

Question 38

What is sickle cell crisis

Answer 38

Fever, dark urine and jaundice due to haemolysis

Question 39

Genetic hypothyroidism

Answer 39

Autosomal recessive

Question 40

2 notable examples of natural selection in genetics?

Answer 40

Sickle cell mutation

Sickle cell heterozygotes have a distinct survival advantage in ares where Plasmodium falciparum is present as the parasite doesnt survive well in sickle cell heterozygote erythrocytes.

CF mutation

Heterozygotes + cholera

Question 41

Triggers for LQT attacks?

Answer 41

Swimming

Auditory stimuli e.g. bell, phone ring

Question 42

What is cascade screening and what is an example of the disease?

Answer 42

Any patient found to have familial hypercholesterolaemia will have the genetic cause idntified and then the test for that mutation is offered to first degree relatives. If those relatives test positive, their first degree relatives are offered it.

Question 43

Lynch syndrome

Answer 43

Autosomal dominant

Question 44

Lissencephaly

Answer 44

X-linked

Question 45

Philadelphia chromosome?

Answer 45

Chronic myeloid leukaemia

Question 46

FAP

Answer 46

AD

APC gene

Knudson’s two hit hypothesis because a germline mutation is inherited which leads to dozens of benign polyps, and a somatic mutation then needs to be acquired in order for the polyp to become cancerous