Genetic disorders
Theme 1: The most significant monogenic diseases
Lecturer MUDr. Marie Černá, CSc.
Cases of single genetic diseases: (pedigree,
clinical manifestation, diagnosis, complication, prognosis, prevention, therapy)
AD:
familial hypercholesterolemia
neurofibromatosis type 1 and 2
hereditary spherocytosis
Disorders associated with defects in structural proteins
Marfan syndrome
achondroplasia
AR:
intestinal lactase deficiency
Disorders of parenchyma organs
polycystosis of kidney
cystic fibrosis
1-antitrypsin deficiency
hemochromatosis
Wilson disease
Disorders associated with defects in enzymes
phenylketonuria and its prevention
alkaptonuria
21-hydroxylase deficiency
Disorders associated with defects in proteins, specific function
sickle cell anemia
thalassemia
XR:
red-green color-blindness
diabetes insipidus renalis
non-spherocytosis hemolytic anemia from G6PD deficiency
Disorders associated with defects in structural proteins
Duchenne and Becker muscular dystrophy
Disorders associated with defects in proteins, specific function
hemophilia A and B
Theme 2: The congenital abnormalities
Lecturer MUDr. Marie Černá, CSc.
1. The most frequent terms in field of population teratology:
teratogen, teratogenic potential, congenital abnormality,
epidemiology of congenital abnormalities, population teratology,
movements of frequencies of congenital abnormalities in time and space – in
one direction long-time movement, accumulation, cluster, cyclic changes –
seasonal and multiyear, nesting and frequency homogeneity – definition,
explanation of term, examples.
2. Teratogenic factors – drugs as teratogens, dividing, establishments,
effects of establishments – database printed/electronic – utilization of WWW.
3. Selected congenital abnormalities – incidence in ČR, international
comparison, definition, etiology, prenatal diagnosis, surviving.
4. Types of congenital abnormalities
–
cleft abnormalities of central nervous system – anencephaly, spina
bifida, encephalocele, congenital hydrocephalus,
–
congenital abnormalities of gastro-intestinal system – oesophageal
atresia, anorectal malformation, intestine stenosis/atresia,
–
congenital abnormalities of kidneys – infantile polycystic kidneys,
renal agenesis/hypoplasia,
–
diaphragmatic hernia, omphalocele, gastroschisis,
–
chromosomal aberration – Down, Edwards, Patau syndromes.
Theme 3: Clinical cytogenetics
Lecturer RNDr. Zdena Polívková
Frequency of chromosome abnormalities in population
Abnormalities of chromosome number: Down syndrome, Patau syndrome,
Edwards syndrome, Turner syndrome, Klinefelter syndrome
– chromosome abnormalities and clinical phenotypes
– prenatal cytogenetic diagnosis
Abnormalities of chromosome structure: review of structural abnormalities:
Cri- du-chat syndrome, Wolf-Hirschhorn syndrome
– chromosome abnormalities and clinical phenotypes
Demonstration of pathological karyotypes with structural abnormalities deletions, duplications, isochromosomes, translocations, inversions, insertions,
complex chromosomal rearrangements, marker chromosomes (chromosomes
stained by G banding technique and fluorescent in situ hybridisation - FISH)
Microdeletion syndromes and syndromes connected with imprinting:
Di George syndrome, CATCH 22, Prader-Willi syndrome, Angelman syndrome
Imprinting and uniparental disomy, their consequences
Fragile X and syndromes connected with trinucleotide repeat instability
Chromosomes in tumors: chronic myelogenous leukemia, Burkitt lymphoma,
retinoblastoma, WAGR association
- demonstration of chromosome abnormalities in tumors, including FISH
Role of cytogenetic in clinical genetics:
chromosomal abnormalities and pregnancy loss,
chromosomal abnormalities in spontaneous abortions
Indications for postnatal and prenatal cytogenetic examination
Theme 4: Genetics of tumor diseases
Lecturer MUDr. Martina Langová
Repetition : Cell cycle regulatory genes, activation of protooncogene to
oncogene, tumor-suppressor genes, mutator genes and diseases
connected with their mutations, viral oncogenes.
Causes of tumor diseases
Multifactorial predisposition of malignancy, risk factors.
Monogenic diseases with higher risk of malignancy.
Connection of chromosomal aberrations with higher risk of malignancy.
Genetic counseling in tumor diseases
Familial incidence of malignity and family history, recommended procedure of
indications, genetic testing and interpretation of results.
Molecular genetic testing in oncological patients, recent possibilities
and trends in genetic testing, predictive testing.
Genetic counseling in families with hereditary forms of malignancy:
Hereditary breast and ovarian cancer – risks, diagnosis, prevention
Recommended medical care of patients with positive mutation
of BRCa 1,2– risks, diagnosis, prevention with breast or ovarian cancer.
Recommended medical care of asymptomatic persons with positive
mutation of BRCa 1,2 – chemopreventin, prophylactic surgery.
Dispensarisation of carriers with BRCa 1,2 mutations in specialized
centers.
Familiar adenomatous polyposis – risks, diagnosis, prevention,
clinical variants of FAP
Hereditary nonpolyposis colorectal cancer (Lynch syndrome) –
risks, diagnosis, prevention
Indication criteria: Amsterdam criteria I a II, Bethesda criteria
Li-Fraumeni syndrome
Molecular basis of disease and genetic counseling.
Molecular biological diagnosis and counseling of some solid tumors in
childhood.