Unit 2 Day 3 Flashcards
chromosome and fish studies are impt. in investigating what?
leukemia and lymphoma
choromosome microarray
standard of complementary to chromosome and fish studies
for individuals with developmental delays
what specimens are used in cytogenetic studies?
bone marrow
blood (unstimulated, constitutional)
tissue (lymph node, solid tumor, poc)
fluids (CNS, amniotic fluid)
what tissues are used in cancer diagnostics
bone marrow unstimulated blood lymph node solid tumor CNS
FISH
fluorescence in situ hybridization single strand probes diffusion signals specific, cloned DNA sequences that enumerate # of specific chromosomes or identify translocations ~200kbp
types of fish probes?
centromere (identifies enumeration)
dual fusion, fusion (identifies translocation)
also: locus specific, break apart, whole chromosome paint
chromosomal in cancer translocations can result in
usually balanced
can end up in site with strong promoters-overexpressed
novel protein creation
where are APMLs seen?
acute myeloid leukemia
granular clumps that form elongated “needles”
what is AML?
acute melodeons leukemia
adults, sometimes children/young adults
translocation 15;17 or translocation 9;22
how do you treat APML?
vitamin a treatment puts into transmission
cleaves conformation of the novel protein that is preventing downstream transcription-allows differentiation to go through
What is CML?
chronic myeloid leukemia
has large lobulated cells
packed bone marrow
how do you treat CML?
targeted, biological therapies
molecular antagonists that bind ATP binding site in abl tyrosine kinase and bcr/abl tyrosine kinase
inhibits cell proliferation
what is the risk for cancer in DS patients?
infants and children have 20-100 fold elevated risk for ALL or AML
500x’s more likely to get AMKL
what is CMA?
Chromosomal Microarray target DNA on slide/chip single stranded oligomers detects gains/losses only limited mosaicism detection (10-15%)
what are the advantages of CMA?
can detect “submicroscopic” gains and losses not seen in FISH
detects hot spot abnormalities
detect abnormalities in backbone of genome
characterize chromosomal anomalies by karyotyping
CNV
copy number variant
CNC
copy number change
what does CMA report?
size, location of deletions/duplications
thresholds of deletions are >200kb, duplications >400kb
evaluate ROH
cannot detect mosaicism, hterodisomy, balanced chromosome rearrangements
Causes of DS
trisomy 21 (95% of patients) unbalanced translocation btw. 21 and acrocentric chromosome (3-4% patients) mosaic tri 21 (1-2% patients), milder phenotype
prenatal counseling approach for DS
- caused by nondisjunction error
- risk increases with maternal age
- 1st trimester prenatal screening (1st trimester, ultrasound measures) (82-87% detection)
- 2nd trimester screening (80% detection), quad screen, unconjugated estriol, inhibit level, ultrasound
- if screen 1st and 2nd, 95% detection
common medical issues of DS
- cardiac issues in 50% patients (Atrioventricular canal, but any heart defect)
- gastrointestinal (10-15% structural anomalies, functional GI issues)
- ophthalmic (v. common)
- ENT problems
- Endocrine problems
- ortho problems
- hematologic issues
- neurologic issues
developmental issues DS
- hypotonia and gross motor defects
- spectrum of intellectual disabilities
- speech issues
what is the spectrum for disability development?
profound (don’t develop past baby)
severe (talk, but not well)
moderate (develop at 1/3 normal rate)
mild (develop at 2/3 normal rate)
Prader-Willi Syndrome medical issues
eyes (strabismus, nystagmus)
ortho (scoliosis)
respiratory (sleep apnea, contraindicates of HGH)
developmentally (mild-mod. cognitive disabilities)
