Lecture 3- More stories from the genetics clinic Flashcards Preview

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Flashcards in Lecture 3- More stories from the genetics clinic Deck (27):
1

What is epigenetic modification? (w.r.t. DNA methylation)

- No change in genetic sequence
- DNA methylation- addition of methyl group to 5' of pyramiding ring of cytosine
- occurs in humans at CpG dinucleotides

2

What does methylation at the gene promoter cause?

Represses gene transcription

3

What is genomic imprinting?

- Non-mendelian inheritance
- the genome carries an imprint or 'stamp' of its parental origin

4

What causes genomic imprinting?

DNA methylation and epigenetic modification

5

List two example of genetic imprinting disorders

Prader-WIlli (Paternal)
Angelman syndrome (Maternal)

6

What are the symptoms of Prader Willi syndrome?

Hyperphagia --> obesity
Mental impairment
Behaviuoral problems
Muscle Hypotonia
Shrort, stature, small hands and feet
Delayed/ incomplete puberty --> infertility

7

How is Prader-WIlli syndrome managed?

- Diet restriction (hyperplasia)
- Exercise to increase muscle mass (hypotonia)
- GH treatment (short stature)
- HRT (for delayed puberty)

8

What are the symptoms of Angelman syndrome?

- development delay and speech impairment
- movement disorder
- Behavioural uniqueness (happy, excitable etc)
- microcephaly
- seizures

9

How is Angelman Syndrome diagnosed?

- Clinica features and molecular diagnosis

10

What is the treatments for Angelman?

Symptomatic- anti-convulsant, physiotherapy, communication therapy

* Normal life span

11

Describe the structure of the mitochondrial genome

- 37 genes
- Code for: tRNA, rRNA, respiratory complexes
- circular DNA
- 2-10 plasmids per mt

12

How are mitochondria inherited?

Through females via oocyte

13

Why can the phenotype of mitochondrial inheritance vary?

Heteroplasmy- cell contains diseased and non-diseased mitochondria

14

Give two examples of mitochondrial disorders

MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes)
LHON (Leber's Hereditary Optic Neuropathy)

15

What are the symptoms of MELAS?

Muscle weakness
Vomiting
Episodic seizures
Headache
Hemiparesis
Dementia

16

How is MELAS diagnosed and treated?

Muscle biopsy
Symptomatic treatment

17

What is the genetic mechanism behind MELAS?

- single mutation in several genes
1) MTTL1: tRNA translates codon as Phe instead of Leu during mt protein synthesis
2) MTND1, MTND5: NADH dehydrogenase subunits 1 and 5

18

What are the symptoms of Lebers?

- degeneration of retinal ganglion cells
- Bilateral, painless, loss of central vision
- Optic atrophy

- average age of onset 20
- more common in males

19

How is Leber's diagnosed?

- ophthalmological findings
- Blood test for mtDNA mutations

20

Which genes might be mutated in LHON?

- MTND1, MTND4, MTND5, MTND6: NADH dehydrogenase subunits
- Cytochrome B MTCYB

21

Which genetic diseases are newborns screened for and how?

Heel prick test
- Sickle cell diseas
- Cystic fibrosis
- Congenital hypothyroidism
- Phenylketonuria
-MCADD

22

What are the symptoms of phenylketonuria?

- lack of melanin
- eczema, musty odour (excess of phenyl acetate)
Can lead to:
- seizures
-severe mental retardation

23

What causes the lack of melanin in PKU?

Tyrosine deficiency

24

What causes severe mental retardation in PKU?

Phenylalanine hydroxylase deficiency --> Phenylalanine accumulation--> converted to phenylpyruvic acid --> excreted in urine

25

What is the treatment for PKU?

- early detection
- remove Phenylalanine from diet
- protein supplements to supply other amino acids
- strict diet in pregnancy

26

What are the symptoms of MCADD?

- Episodic hypoketotic hypoglycaemia
- Vomiting, coma, metabolic acidosis, encephalopathy
- 25% mortality if undiagnosed

27

What is the treatment for MCADD?

- avoid fasting
- nutritional supplements