Genetics 3- More stories from the genetics clinic Flashcards
Which base is methylated in gene imprintation
Cytosine
this switches off
What is Prader Willi syndrome
8 Symptoms
Management
fault in Paternal gene- maternal silienced
Symptoms: Hyperphagia Obesity/Diabetes Mental Retardation Muscle Hypotonia Short Stature Small Hands and Feet Delayed/Incomplete Puberty Infertility
Management: -by symptoms Hyperphagia managed by diet restriction Exercise to increase muscular mass Growth hormone treatment for short stature Hormone replacement at puberty
What is the Genetic Mechanism of Prader-Willi Syndrome
Caused by the lack of a functional paternal copy of the PWS critical region on 15q11-q13.
70% due to deletion of the critical region on the paternal chromosome
25% due to inheritance of two maternal copies by uniparental isodisomy
5% due to other mechanisms such as translocations
Uniparental Isodisomy
Ending up with a zygote that has a pair of chromosomes from one parent not both.
What is Angelman Syndrome
6 symptoms
fault in maternal gene- paternal silenced
Symptoms: Severe Developmental Delay Poor or Absent Speech Gait Ataxia 'Happy Demeanour' Microcephaly Seizures
Treatment is Symptomatic:
Anti-Convulsant
Physiotherapy
Communication Therapy
Explain Mitochondrial Inheritance
ONLY TRANSMITTED THROUGH FEMALES
The ovum has mitochondria. When the sperm meets the ovum, it loses its mitochondria and only the DNA gets through.
Mitochondrial disease affects males and females.
Different cells have different energy requirements and so vary in the number of mitochondria.
Heteroplasmy - The situation in which, within a single cell, there is a mixture of mitochondria (energy producing cytoplasmic organelles), some containing mutant DNA and some containing normal DNA.
What isMELAS - Mitochondrial myopathy, Encephalopathy, Lactic Acidosis and Stroke
5 symptoms
What is the diagnosis
Progressive neurogenerative disorder
Symptoms: Muscle Weakness Episodic Seizures and Headache Hemiparesis Vomiting Dementia
MELAS affects the muscles and the brain because they both have high energy requirements and hence a lot of mitochondria.
MELAS and the brain:
Treatment is symptomatic
Diagnosis is by muscle biopsy
Genetics - Single Mutations in several genes:
LHON - Leber’s Hereditary Optic Neuropathy
2 symptoms
Diagnosis
For unknown reasons - more common in males.
Affects people on average in their mid 20s to mid 30s.
Symptoms:
Bilaterial, painless, loss of central vision
Optic Atrophy This eventually leads to BLINDNESS.
Treatment is symptomatic
Diagnosis:
Ophthalmological Findings
Blood Test for mtDNA Mutations
Genetics
What 5 disorders are screened for
Phenylketonuria
Congenital Hypothyroidism
Sickle Cell Disease
Cystic Fibrosis
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD Deficiency)
Describe Phenylketonuria (PKU)
5 symptoms
Treatments/diagnosis
Symptoms
Severe Mental Retardation and Convulsions
Blonde Hair/Blue Eyes
Eczema
Phenylalanine Hydroxylase Deficiency (causes the severe mental retardation)
phenylpyruvic acid - excreted in urine.
Tyrosine Deficiency - reduced melanin
Treatments/diagnosis
Early Detection = No Mental Retardation, no convulsions (essentially no ill effects at all)
You screen for elevated levels of phenylalanine in the blood.
Then you remove phenylalanine from the diet if you suspect that the patient has PKU.
Describe MCAD (Medium Chain Acyl-CoA Dehydrogenase) Deficiency
How do symptoms present
Mortality rate
Solutions
Commonest disorder of fatty acid oxidation.
Symptoms
Episodic Hypoketotic Hypoglycaemia
Presents as: Coma, Metabolic Acidosis, Encephalopathy
Sudden Death can occur - 25% mortality rate in undiagnosed cases
MCAD Deficiency Management
Can be detected using bloodspot
SOLUTION: Maintenance of adequate calorie intake to prevent switch to fatty acid oxidation.
AVOID FASTING (>12 hours) - difficult in children who lose their appetite due to illness - honey or glucose drip
