Genetic diseases

Question 1

What are some examples of autosomal dominant diseases?

Answer 1

• Huntington disease
• Myotonic dystrophy
• Polycystic kidney disease
• Ehlers Danlos syndrome

Question 2

What is Ehlers Danlos syndrome and what is its cause?

Answer 2

• Connective tissue disorder.
• Symptoms include:
  1. Bruising easily
  2. Thin skin
  3. Fragile blood vessels
  4. Easily damageable hollow organ
• Caused by mutations in collagen gene (esp. COL3A1)

Question 3

What are some examples of autosomal recessive diseases?

Answer 3

1. Cystic fibrosis
2. Spinal muscular atrophy
3. Congenital adrenal hyperplasia

Question 4

What are some examples of numerical abnormalities?

Answer 4

• Turner syndrome: XO
• Down syndrome: Trisomy 21
• Edward’s syndrome: Trisomy 18

Question 5

What is the cause of Down syndrome?

Answer 5

• Trisomy 21
• Result of chromosome non-disjunction
• Most commonly occurs during meiosis, especially during egg formation
• > 90% of cases inherited maternally
• Risk of non-disjunction and thus acquiring the disease increases as maternal age increases

Question 6

What is an example of disease causing insertion/deletion?

Answer 6

• 22q.11.2 deletion syndrome.
• Causes schizophrenia and other associated neurological disorders.
• Causes DeGeorge’s syndrome.

Question 7

What is an example of disease causing reciprocal translocation?

Answer 7

• Philadelphia chromosome.
• Balanced translocation between chromosomes 9 and 22.
• Found in ~95% of patients with chronic myeloid leukaemia.

Question 8

What are the common genetic disorders caused by sex chromosome non-disjunction?

Answer 8

1. Turner’s syndrome (45 XO)
2. Klinefelter’s syndrome (47 XXY)
3. XYY male

Question 9

What are the symptoms of Turner’s syndrome?

Answer 9

• Webbed neck
• Short
• Infertility

Question 10

What are the symptoms of Klinefelter’s syndrome?

Answer 10

• Tall and thin
• Gynecomastia
• Learning impairment (mild)
• Infertility

Question 11

What are examples of X-linked recessive disorders?

Answer 11

1. Duchenne muscular dystrophy
2. Haemophilia
3. Red-green colour blindness

Question 12

What are the causes and symptoms of DMD?

Answer 12

• Mutation in Dystrophin gene on X-chromosome

- Progressive muscle weakness and degeneration

Question 13

What are the causes and symptoms haemophilia?

Answer 13

• Haemophilia A: Factor VIII affected
• Haemophilia B: Factor IX affected
• Ineffective blood clot formation results in excessive bleeding.

Question 14

What is an example of an X-linked dominant disorder?

Answer 14

• Rett syndrome.
• Caused by a mutation in MeCP2 gene, which makes protein involved in methylation.
• Associated with neurological disorders such as seizures, inability to talk and hand movements.

Question 15

What is Campomelic Dysplasia?

Answer 15

• Mutation of SOX9 gene on chromosome 17.

- Causes sex reversal and skeletal dysplasia in males.

Question 16

What are the diseases associated with maternal uniparental disomy?

Answer 16

• 7: Silver-Russell syndrome
• 11: Silver-Russell syndrome
• 14: Maternal UPD14 syndrome (Temple syndrome)
• 15: Prader-Willi syndrome

Question 17

What are the diseases associated with paternal uniparental disomy?

Answer 17

• 6: Transient neonatal diabetes
• 11: Beckwith-Weidemann syndrome
• 14: Paternal UPD14 syndrome (Kagami-Wang syndrome)
• 15: Angelman syndrome

Question 18

What is Beckwith-Weidemann syndrome?

Answer 18

• Paternal uniparental disomy of chromosome 11.
• Foetal overgrowth with increased risk of childhood tumours.
• Overexpression of IGF2 in placental cells (paternal).
• No expression of CDKN1C (maternal).

Question 19

What is Angelman syndrome?

Answer 19

• Paternal uniparental disomy 15.
• Severe developmental delays.
• Ataxic movement.
• Short attention spans.
• No expression of UBE3A.

Question 20

What is Silver-Russell syndrome?

Answer 20

• Maternal uniparental disomy 7/11.

- Slow pre-/postnatal growth.

Question 21

What is Prader-Willi syndrome?

Answer 21

• Maternal uniparental disomy 15.
• Neurological problems such as hypotonia, respiratory difficulties, sleeping disorders…
• Excess weight gain
• Delayed weight gain

Question 22

What are examples of mitochondrial diseases?

Answer 22

1. DIDMOAD
2. Kearns-Sayre syndrome
3. LHON

Question 23

What are examples of trinucleotide expansion diseases?

Answer 23

• Fragile-X syndrome: Caused by CGG repeat
• Myotonic dystrophy: Caused by CTG repeat
• Huntington disease: Casued by CAG repeat
• Friedreich ataxia: Caused by GAA repeat

Question 24

What causes fragile-X syndrome?

Answer 24

• CGG repeat on exon 1 of FMR1 gene on X-chromosome.
• TNEs prevent the FMR1 gene from being transcribed, preventing the production of FMRP, which is essential in cognitive development.

Question 25

What are the symptoms of fragile-X syndrome?

Answer 25

- Learning disabilities - Long face/large ears - Increased risk of seizures - Autism

Question 26

What causes Friedreich's ataxia?

Answer 26

- GAA repeats on intron 1 of Frataxin gene on chromosome 9. - Trinucleotide repeats cause increased epigenetic modifications (including histone modifications) to the Frataxin gene, suppressing its transcription and expression.

Question 27

What are the symptoms of Freidreich's ataxia?

Answer 27

1. Speech and movement abnormalities 2. Heart disease 3. Diabetes

Question 28

What causes myotonic dystrophy?

Answer 28

- CTG repeats on 3’ end of DMPK gene in chromosome 19. - Accumulation of abnormal pre-mRNA sequesters RNA-binding proteins and prevents them from carrying out their normal functions (alternative splicing).

Question 29

What are the symptoms of myotonic dystrophy?

Answer 29

1. Progressive muscular dystrophy | 2. Myotonia (difficulty relaxing muscles post-contraction)

Question 30

What causes Huntington's disease?

Answer 30

- CAG repeats in Huntingtin gene in chromosome 4. - CAG repeats sequence causes polyQ (Gln) strand in Huntingtin protein. - PolyQ sequences in Huntingtin gene cause formation of polyQ-huntingtin aggregates when the protein is cleaved. - Aggregates damage mitochondria, leading to the stimulation of apoptosis.

Question 31

What are the symptoms of Huntington's disease?

Answer 31

1. Intellectual decline 2. Myoclonus 3. Dystonia 4. Dementia