CS: Genetics Flashcards
Tall, long fingered, downward lens dislocation, learning difficulties, DVT
- homocystinuria AR
brown/bluish pigment of the ear cartilage or sclera, arthropathy, renal stones, cardiac valve involvement and coronary calcification.
Alkaptonuria AR
Men with BRCA mutations have an increased risk of
Prostate Ca
APC gene is responsible
colorectal tumours in which ras and p53 mutations are also often involved.
Li-Fraumeni syndrome Sx (5)& Gene
Rare AD, mutation in the P53 gene-
- soft tissue sarcomas,
- breast carcinoma,
- glioblastoma,
- lymphoma
-leukaemia.
Tall, long fingered, downward lens dislocation, learning difficulties, DVT
AR
Homocystinuria
Friedreich’s ataxia inheritance
AR
Oncogene ABL
Cytoplasmic tyrosine kinase Chronic myeloid leukaemia
Oncogene c-MYC
Transcription factor
Burkitt’s lymphoma
Oncogene n-MYC
Transcription factor Neuroblastoma
Oncogene BCL-2
Apoptosis regulator protein Follicular lymphoma
Oncogene RET
Tyrosine kinase receptor Multiple endocrine neoplasia (types II and III)
Oncogene RAS
G-protein
Many cancers especially pancreatic
Oncogene erb-B2 (HER2/neu)
Tyrosine kinase receptor
Breast and ovarian cancer
Oncogenes
- gain of function results in an increased risk of cancer
Tumor suppressor genes
- loss of function results in an increased risk of cancer
Developmental delay
Cherry red spot on the macula, without hepatomegaly or splenomegaly
Tay-Sachs disease is a type of lysosomal storage disease
hepatosplenomegaly, cherry red spot on the macula
Niemann-Pick disease
angiokeratomas, peripheral neuropathy of extemeties, renal failure
Fabry disease
hepatosplenomegaly, aseptic necrosis of the femur
Gaucher’s disease
mitochondrial inheritance
onset < 20-years-old
external ophthalmoplegia
retinitis pigmentosa
Kearns-Sayre syndrome
proteinuria, early onset strokes or MI with a typical rash known as angiokeratomas
Fabry disease
X-linked recessive
Screening for haemochromatosis
- Gen pop
- Family members
general population: transferrin saturation > ferritin
family members: HFE genetic testing
Associates with T8:14
- Burkitt’s Lymphoma - 8 c-myc (oncogene) + 14 Ig heavy constant region
T14:18
- Follicular Lymphoma - 14 Ig heavy constant region + 18 Bcl2 (anti-apoptotic gene)
14teen-culr lymphoma
T15:17
- Acute pro-myelocytic leukaemia - 15 Promyelocytic gene + 17 Retinoid acid receptor alpha (Fusion protein binds retinoid acid receptor and promotes transcription).
T11:14
- Mantle Cell Lymphoma - 11 - Cyclin D (oncogene) + 14 Ig heavy constant region
t(15;17)
Good prognosis AML
Alport’s syndrome inheritance
X-linked dominant
What is RT PCR used for ?
Identify specific units of mRNA
Genetic abnormality and symptoms of kleinfelters
47 XXY
Tall, infertile, gynaecomastia, small hard testes, lack secondary sexual characteristics, increased gonadotropin levels
What is the pathology of Kallman’s syndrome?
features?
x-linked recessive
failure of GnRH secreting neurones to migrate down into hypothalamus
what is the enzyme deficiency in homocystinuria?
what is the amino acid affected?
cystathionine beta synthase (CBS) deficiency
what are the features of pseudoxanthoma elasticum?
auto rec abnormality in elastin fibres
plucked chicken skin appearance - small yellow papules on neck and axillae
retinal angoid streaks
cardiac: mitral valve prolapse, increased risk of IHD
GI haemorrhage
Ix and Rx of Wilson’s disease
Dx: low caeruloplasmin, raised urinary copper excretion
Mx: penacillamine or trientine (chelates copper)
Thalidomide
SE
Uses
Irreversible neuropathy
teratogenic
drowsiness
Constipation and
weight gain
it’s used to treat leprosy HIV multiple myeloma
Inheritance of sickle cell and what is the substitution?
AR
Substitution of valine for glutamic acid
HNPCC/ Lynch syndrome-
Causes
Genes and inheritance
Amsterdam criteria
most common form of inherited colon cancer. Usually the proximal colon, which highly aggressive.
Higher risk of other cancers (endometrial cancer most common) The most common genes involved are:
- MSH2 (60% of cases)
- MLH1 (30%)
The Amsterdam criteria are sometimes used to aid diagnosis: - at least 3 family members with colon cancer
- the cases span at least two generations
- at least one case diagnosed before the age of 50 years
Familial Adenomatous polyposis –
-Inheritance
-Predominant distributions
- Mutation
- Rx
AD
> 100 polyps before 40 y.o = carcinoma
- predominantly left sided distribution.
-mutation APC tumour suppressor gene on chromosome 5.
RX total colectomy with ileo-anal pouch formation in their twenties.
Gardner’s syndrome feature
AD
Type of FAP
feature
osteomas of the skull and mandible,
retinal pigmentation,
thyroid carcinoma and
epidermoid cysts on the skin
ADAMTS -2 gene mutation is ass w/
Ehlers-Danlos
Wiskott-Aldrich syndrome
Defective gene
Inheritance
Features (7)
Wiskott-Aldrich syndrome
-Defect in WASP gene
- X-linked recessive. Variable penetrance
-recurrent bacterial infections,
-eczema,
-thrombocytopaenia.
-Low IgM levels
-Increased risk of autoimmune disorders and
-malignancy
Inheritance of Majority compliment deficiencies
AR
Von Hippel-Lindau (VHL)
Inheritance and gene
Features (5)
Von Hippel-Lindau (VHL)
AD
VHL gene on chromosome 3
Features
1. cerebellar haemangiomas: these can =SAH
2. Retinal haemangiomas: vitreous haemorrhage
3. renal cysts (premalignant)
4. phaeochromocytoma
5. extra-renal cysts: epididymal, pancreatic, hepatic
endolymphatic sac tumours
clear-cell renal cell carcinoma
BRCA1 function
DNA repair
What is Aneuploidies
cell has an extra or missing chromosome.
most common aneuploidies in humans (3 trisomies)
Trisomy 21 (Down syndrome), Trisomy
Trisomy 13 (Patau syndrome).
18 (Edwards syndrome),
least common and most severe trisomy
Patau syndrome (trisomy 13)
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
Edward’s syndrome (trisomy 18) SX
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
Fragile X sx
- Fragile X (CGG)- X-linked dominant pattern
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism
Noonan syndrome
AD
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
Pierre-Robin syndrome*
De novo
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
Prader-Willi syndrome
Hypotonia
Hypogonadism
Obesity
narrow forehead, almond-shaped eyes, and a triangular mouth; short stature; and small hands
William’s syndrome
chromosome 7
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
