Genetics Flashcards
How is Marfan’s inherited
autosomal dominant
Which gene is mutated in Marfan’s
missense mutation in chromosome 15q21
Codes for fibrillar FBN 1
Clinical presentation of marfan’s
Tall
Down slanting palpebral fissures
Aorta root dilatation and dissection
Mitral valve prolapse
spontaneous pneumothorax
How is CF inherited
Autosomal recessive disorder of exocrine gland function
What gene is mutated in CF
CFTR gene found on chromosome 7
Function of CFTR
ATP responsive chloride ion channel
Inhibits epithelium Na channels
How dose mutation of CFTR cause CF symptoms
Resp. epithelium fai to secrete Chloride ions and hyper absorbs Na ions and water -> dehydration of airway surface
surface becomes sticky
Cillia can’t work probably - bacteria grow
Pancreas in CF
Enzymes are produced but can’t be released due to defects in channels -> causing dehydration of pancreatic secretions
Presentation of CF in newborn
Positive new born screening test
meconium ileum
jaundice
pseudo-barter syndrome (hypochloremaic, hypokalaemia alkalosis)
hypoalbuniemia
Other presentation of CF
Recurrent chest infections - teenages pseudomonas
Bronchiectasis
steathorrea
faltering growth
diabetes
Nasal polyps
Distal intestinal obstruction
Infertility - 99% of males
Newborn screening test in relation to CF - what is raised
immunoreactive trypsin - raised in first 6 weeks of life with CF
Other Ix for CF
Sweat test - chloride ions >60 is diagnostic
Molecular gene testing
Treatment for CF
Chest physio - minimum twice daily
hypertonic 7% saline
long-term nebuliser ABX - colomycin / tobramycin
Proph. oral antibiotics
Creon
Calcium replacemnet
How many people carry CF mutation
one in 25
Galactosemia features
Jaundice - conjugated
Hepatomegaly
Oil-drop cataracts
Ass. coagulopathy and E.Coli sepsis in neonates
How Is galactosemia inherited
autosomal-recessive
What gene has a mutation in galactosemia
mutations and deficiency of galactose-1-phosphate uridyltransferase GALT enzyme
What function can’t happen in galactosemia
Can’t metabolise galactose or lactose
Management of galactoseamia
Lifelong diet modification
lactose and galactose free diet
What are Trisomy 18 (Edwards syndrome) dysmorphic features
Large occiput
rocker-bottom feet
Overlapping digits
Newborns with Trisomy 18 features
Micrognathia
IUGR
Hypertonia
small mouth
Trisomy 18 ass. features
cataracts
DDH
congenital heart disease - ventricular septal defects
diaphragmatic hernia
Renal abnormalities - horseshoe kidney
What is Tay-Sachs disease?
neurodegenerative lysosomal storage disorder
How is Tay-Sachs disease inherited?
autosomal-recessive disorder
More common in Ashkenzai Jewish descent - 1/250 to 1/300
How is CAH inherited
Autosomal recessive
What does Gilbert syndrome cause?
Isolated unconjugated high bilirubin
Normal LFT’s
No heamolysis
Autosomal recessive
What mutation is found in Gilbert’s Syndrome
UGT1a1 gene located on 2q37
Reductive in production of enzyme UDP-UGT which is responsible for the conjugation of bilirubin
What is most common cause of Prader-willi syndrome
deletion of paternal chromosome 15q11-q13
maternal uniparental disomy 15
Presentation of Prader-Willi syndrome
severe neonatal hypotonia
Difficulties feeding
Weight gain
Short stature - growth hormone defiency
Facial features - narrow forehead, almond shaped eyes, thin upper lip, down turned mouth
Hypogonadism
Hypothyroidism
Learning disabilities
What do you need to test for diagnosis of Prader-Willi syndrome
DNA methylation analysis
What type of genetic mutation is in myotonic dystrophy
trinucleotide nuclear expansion
What gene is involved in Retts Syndrome
MECP2
How is nuerofibromatosis type 1 inherited
Autosomal dominant
Half are de novo mutation
Presentation of NM1
Cafe au lait
Axillary / groin freckles
Lisch nodules- raised tan coloured haemartomas of the iris
ossesous lesions
hTN
Neurofibromas - more common in adolescents and adults
Cognitive impairment
Differences between NF1 and NF2
NF2 never has cafe-au lait spots
axillary and groin freckles not common in nF2
Lish nodes diagnostic of NF1
Neurofibromas in NF1, NF2 swahanomas and neurilemmonas
NF2 not ass. with cognitive impairment
How are mutations in mDNA inherited?
Mother inheritance
How are mutations in nDNA inherited?
Follow autosomal dominant / autosomal recessive / X linked pattern
Age of onset of mDNA mutations
adults
Age of onset of nDNA mutations
children
Is lactic acidosis more common to be seen in mDNA or nDNA mutations
mDNA
What to primary mitochondria disorders lead to ?
Decrease in ATP production
Increase in reactive oxidative spieces (ROS) = leads to state of oxidative stress
Increase ROS damage mtDNA and nDNA, protein and lipid oxidation have bad affect on multiple organ systems
What does array comparative genomic hybridisation (aCGH) look for?
Chromosomal copy number variations
Compares patient DNA to control DNA
Detects deletions and duplications
What does fluorescence in situ hybridisation FISH look for?
Allows for targeted investigation of copy number variations and structural rearrangements
Only detects abnormalities in region targeted by chosen probe
Trisomy 13 - Patau syndrome features
Closely-spaced eyes
Midline cleft lip and palate
Holoprosencephaly
Polydactyly
Cardiac abnormalities
What mutation causes DiGeorge syndrome?
Deletion at 22q11 region of one copy of chromosome 22
Majority of cases De Novo
Autosomal dominant
Name conditions that are inherited in Autosomal dominant method?
Myotonic dystrophy
Achondroplasia
Tuberous sclerosis
NF1
Marfans syndrome
Name conditions that are Imprinting disorders
Beckwith-Wiedemann syndrome
Angelman syndrome
Prader-Wili syndrome
Albight’s hereditary oestodystropgy
DiGeorge syndrome characteristics
Short stature
transient neonatal hypocalcemia
Cleft palate
Abnormalities with T cell function
TOF
Cause of DiGeorge syndrome
deletion of 22q11
De Novo
Cause of Angelman Syndrome
Paternal uniparental disomy of chromosome 15
Gene codes for UBE3A
Inherits both copies from Dad - none from mum
Angelman Syndrome characteristics
Ataxia
Happy disposition
Wide mouth
Microcephaly
Beckwith-Wiedemann Syndrome
Abnormalities at the imprinted 11p15 growth regulatory region
Paternal uniparental disomy at chromosome 11p15
Beckwith-Wiedemann Syndrome features
pre- post natal overgrowth
neonatal hypoglycaemia
coarse facial features
exomphalos
earlobe creases
Increase risk of wilms tumour
How is Lesch-Nyhan syndrome inherited
X-linked disorder
Features of Lesch-nyhan syndrome
Gout
gross motor delay
self-mutilating behaviour
What happens in Lesch-nyHan syndrome
Over production of uric acid
Features of William’s syndrome
Mild microcephaly
Learning disabilities
Talkative - can usually hide degree of difficulty
What is HLA b27 related with?
Reactive arthritis
Ank spondylitis
What is HLA B47 associated with?
21 hydroxylase defiency
What is HLA CW6 associated with?
psoriasis
What is HLA DR2 associated with?
multiple sclerosis
SLE
Criger- Najjar signs
severe unconjugate hyperbole
What mutation is found in Criger-Najjar syndrome
mutations in UGT1A1
Leads to enzyme defect involved in converting unconjugated to conjugated
Autosomal recessive
What is first line test for global development delay
microarray
Incontinentia pigmenti
X-linked dominant
Linear cuteanous lesion that start blistering rash at birth - > become wart like growth and hypigmentation
What is anticipation
Increase length of unstable area in gene - longer unstable area of gene, more severe and earlier disease progression
Myotonic dystrophy
What gonadal mosaicism
Parents have mutation in germ cells and not in somatic cells
Achondroplasia
Osteogenesis imperfecta
Duchenne muscular dystrophy
Fragile X - trinucleotide expansion
cytosine-guanine - guanine C-G-G
Why does SMA occur
degeneration of alpha motor neurones in anterior spinal horn of spinal cord
deletion or mutation in SMN1 gene
Autosomal recessive
Di George Syndrome - Catch 22
Cardiac
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcaemia / hypoparathyroidism
Microdeletion of 22q11.2
Southern blotting
Presence of absence of specific DNA fragments in mixture of DNA
Noonan sydnrome mutation
PTPN11
Cri-du-CHat
High pitch scream
5p deletion
