Clinical Genetic Testing

Question 1

genetic testing in order of increasing resolution

Answer 1

karyotype -> aCGH and FISH -> PCR

Question 2

What do NORMAL cytogenetic findings mean

Answer 2

• *non-diagnostic
• abnormal cells could still be present at low level (ie mosaicism)
• genetic changes may be present, but too small to see
• tumor cells may not have grown in culture

Question 3

all patients with turner syndrome diagnosis need

Answer 3

• cardiology consult
• renal ultrasonography
• audiology eval
• examination for scoliosis/kyphosis
• growth and pubertal development tracking
• annual BP check
• re-eval by ENT/audiology 1-5 years
• genetic counseling

Question 4

growth in turner syndrome

Answer 4

• they are not growth hormone deficient, but need suprpahysiological doses to drive growth
• may also need estrogen and anabolic steroid (normalize 2° sex characteristics, bone/mineral, heart, brain, liver function

Question 5

turner syndrom reproductive

Answer 5

• streak ovaries may be present at birth
• if normal 46, XX ovaries: oocytes decrease from 6 mil to 2 mil by birth
• most don’t have spontaneous puberty
• risk of spontaneous abortus (SAB) high

Question 6

genetic testing for turner syndrome

Answer 6

• karyotype, FISH, CGH
• FISH recommended to look for y chromosome material
• if y chromosome material found, prophylactic gonadectomy recommended b/c risk of gonadoblastoma high

Question 7

key points about FISH

Answer 7

• permits detection of small cytogenetic changes invisible to karyotype
• can detect translocations
• can be performed on metaphase chromosomes or interphase nuclei
• VERY SPECIFIC

Question 8

LCR

Answer 8

• low copy repeats=repetitive DNA
• may facilitate crossing over
• various genomic changes can be catalyzed by LCRs, including deletions, duplications, and inversions

Question 9

copy number variants (CNVs)

Answer 9

a change found in CGH that does not seems to affect phenotype

Question 10

what is a weakness of CGH

Answer 10

• cannot detect balanced translocations

* it detects gain or loss of genetic material

Question 11

key points of CGH aka chromosomal microarray

Answer 11

• combines resolution of FISH and scope of karyotype
• competitive hybridization of patient and control DNA to an array
• benign CNVs complicate interpretation; results sometimes inconclusive

Question 12

PTEN gene syndromes

Answer 12

• cowden syndrome
• bannayan-riley-ruvalcaba syndrome
• proetus syndrome (PS)
• proteus-like syndrome (PLS)

Question 13

Juvenile polyposis syndrome (JPS)

Answer 13

• BMPR1A gene
• juvenile refers to the type of the poly, not age of onset
• bleeding and anemia
• most polyps benign, but malignant transformation can occur
• found in GI tract, specifically stomach, small intestine, colon, and rectum
• Can be found with CGH