Reproductive Genetics

Question 1

those with low MCV and normal hemoglobin electrophoresis without iron deficiency anemia are at risk of

Answer 1

alpha thalassemia. partner testing should be offered.

Question 2

iron deficiency anemia can mislead clinicians, iron deficiency anemia can be diagnosed via

Answer 2

serum ferritin, zinc protoporphyrin

Question 3

most places use MCV value of 80 as cutoff. others suggest in high prevalence areas, a cutoff of

Answer 3

85

Question 4

(–/–)

Answer 4

Barts ; mcv <80

Question 5

(a-/–)

Answer 5

hemoglobin H disease mcv<85 alpha thalassemia trait hypochromic/microcytic anemia

Question 6

(a-/a-)

Answer 6

African (trans)

Question 7

(–/aa)

Answer 7

SE Asian (cis)

Question 8

beta thalassemia has

Answer 8

mcv3.5%)

Question 9

Fragile X

Answer 9

most common form of inherited mental retardation, those affected often have cognitive disability, craniofacial dysmorphisms, speech and language difficulties, and behavior abnormalities such as autism or autistic-like features.

Question 10

fragile X inherited in an

Answer 10

x-linked manner. fragile X occurs secondary to hypermethylation and results in an alterted transcription of the Fragile X mental retardation 1 (FMR1) gene

Question 11

women with premutations are at increased risk for

Answer 11

premature ovarian failure and having an affected child.

Question 12

males are at risk of late-onset neurodegenerative disorder characterized best by tremor and ataxia this condition is known as

Answer 12

Fragile X- Ataxia (FXTAS)

Question 13

who should be offered carrier screening for Fragile X?

Answer 13

women with family hx of Fragile X, autism, unexplained learning disability / unexplained mental retardation.
2. offer screening to all women with a personal hx of learning disability, premature ovarian failure, or elevated follicle-stimulating hormone (FSH) at age <40.

Question 14

SMA spinal muscular atrophy

Answer 14

2nd most common fatal autosomal RECESSIVE disorder.

Question 15

SMA leads to progressive muscle weakness and paralysis.

Answer 15

the alpha motor neurons in the anterior horn of spinal cord are afected.

Question 16

SMA characterized by 3 clinical courses:

Answer 16

1. SMA I (Werdnig-Hoffman) most severe and typically results in death secondary to respiratory failure at 2 years of life.
2. Survival improves in those affected with SMAII, bu children unable to sit/stand/walk unaided. this is most common form. these individuals often die of respiratory failure in adolescence.
3. SMAIII (Kugelberg-Welander) are able to learn to walk unaided, and onset usually occurs after 18 months. may have normal life expectancy.

Question 17

SMA caused by

Answer 17

deletion on both copies of SMN1.

Question 18

risk of invasive prenatal diagnosis: procedure related loss caused by invasive testing has traditionally been quoted as

Answer 18

1:200, but recent studies indicate this is an overestimation. approximately 1 in 300 to 500 in experienced centers.

Question 19

Early CVS (<14 wks) can be associated with

Answer 19

increased rates of malformations / pregnancy loss.

Question 20

Chorionic villus sampling (CVS) procedure related pregnancy loss rate:

Answer 20

loss rate after CVS will always e higher than amnio secondary to increased background loss rate at earlier gestational age.

Question 21

CVS should not be performed <9 weeks

Answer 21

limb reduction defects and oromandibular hypoplasia has een associated with early CVS <7 wks.

Question 22

maternal complications after CVS:

Answer 22

vaginal spotting / bleeding in 30-35% of pts.

infection or amniotic fluid leakage approx 0/5% after CVS

Question 23

early amnio <14 weeks results in higher rates of miscarriage and other complications such as talipes equinovarus.

Answer 23

true

Question 24

other risks of amnio:

Answer 24

1. leakage of fluid in <1% of all specimens.

Question 25

Arrah CGH. Conventional karyotype remains gold standard for chormosome # and structural abnormalities. Chromosomal microarray is promising technique that can detect clinically significant deletions and duplications on cultured/ uncultured material at higher resolution more rapidly compared with conentional karyotype.

Answer 25

true

Question 26

conventional karyotype detects the following:

Answer 26

1. whole chromosome aneuploidy, which is defined as abnormal # of chromosomes such as trisomy 21. 2. very large deletions/ duplications (>10-15Mb of chromosomal material), 3. balanced translocations

Question 27

microarray utilizes comparative genomic hybridization, is a chip based technology that has much higher resolution, and is able to

Answer 27

scan the genome for submicroscopic copy # variation that is missed by conventional karyotyping. microarray will be able to identify submicroscopic deletions and duplications that conventional prenatal chromosome analysis cannot pick up.

Question 28

despite higher resolution, Array CGH has limitations

Answer 28

microarray does not detect balanced rearrangements such as balanced translocations or inversions because there is no gain or loss of genomic material. microarray does not detect triploidy or tetraploidy.

Question 29

umbilical cord blood contains

Answer 29

hematopoietic stem cells, which could potentially be used for future transplantation.

Question 30

disorders that could potentially benefit from hematopoietic stem cell transplantation :

Answer 30

inborn errors of metabolism, hematopoietic malignancis, genetic disorders of blood and immune system

Question 31

private cord blood banks?

Answer 31

if child develops leukemia or inborn error of metabolism, the unit could NOT be used to treat that child, as these abnormalities would be present in stem cells. Likelihood of using autologous unit of blood is estimated to be 1 in 2,700 or potentially even lower. recent cost-effectiveness analysis found that private cord blood banking was not cost effective and would become cost effective if entire cost of blood banking was $262 or less or risk of child requiring a hematopoietic stem cell transplantation was more than 1 in 110.

Question 32

Noninvasive Diagnosis of FEtal Material

Answer 32

helpful in determination of fetal RhD status or sex to determine if fetus is at risk for isoimmunization or an x-linked disorder.