HRR: genetic screening II

Question 1

What are the two highest populations with CF?

Answer 1

Caucasian and AJ

Question 2

What is the inheritance of CF?

Answer 2

Autosomal recessive

Question 3

How does CF impact fertility?

Answer 3

Causes infertility in 95% of males who have it

Question 4

How do we screen for CF?

Answer 4

Complete CFTR gene sequencing

Question 5

Who do we screen for CF?

Answer 5

All patients who are pregnant or considering pregnancy

Question 6

What is the inheritance of fragile X?

Answer 6

X linked

Question 7

Who do we screen for fragile X?

Answer 7

1. Women with a family history of it
2. Women with a family history of unexplained intellectual disability, developmental delay, or autism
3. Women with ovarian insufficiency or elevated FSH before 40 without known cause
4. Adults with late onset tremor and ataxia of unknown cause

Question 8

What gene is associated with fragile X?

Answer 8

Trinucleotide repeat extension in FMR1 gene

Question 9

What are manifestations of fragile X?

Answer 9

Abnormal facial structure, behavioral abnormalities and autism, intellectual disability, connective tissue problems

Question 10

How many repeats are needed for full mutation in fragile X?

Answer 10

More than 200

Question 11

How many repeats can you have and be unaffected by fragile X?

Answer 11

Less than 45

Question 12

What is considered premutation for fragile X?

Answer 12

55-200 copies

Question 13

Describe a basic hemoglobin.

Answer 13

2 alpha units, 2 beta units, and 4 oxygen binding heme groups

Question 14

Which genes encode the alpha globin?

Answer 14

Genes on chromosome 16

Question 15

Which genes encode the beta globin?

Answer 15

Genes on chromosome 11

Question 16

What gene is associated with sickle cell disease?

Answer 16

Homozygous mutation in HBB (beta globin gene)

Question 17

What are issues associated with sickle cell disease?

Answer 17

Vaso-occlusion, chronic hemolytic anemia, organ damage, destroyed spleen, infections

Question 18

What is the inheritance pattern of sickle cell disease?

Answer 18

Autosomal recessive

Question 19

Who is most likely to have sickle cell?

Answer 19

Black population

Question 20

What is recommended by ACOG in terms of hemoglobinopathy carrier screening?

Answer 20

Include CBC and hemoglobin electrophoresis for anybody as a starting point for hemoglobinopathies

Question 21

What is thalassemia?

Answer 21

Reduced production of specific globin chain

Question 22

What are the types of alpha thalassemia?

Answer 22

Hemoglobin Bart hydrops fetalis and hemoglobin H disease

Question 23

Describe hemoglobin Bart hydrops.

Answer 23

A severe form in which no alpha globin is being produced. Characterized by fetal edema, pleural and pericardial effusion, and severe hypochromic anemia

Question 24

Describe hemoglobin H disease.

Answer 24

Some alpha globin is being made. Can result in hepatosplenomegaly, mild jaundice, microcytic hypochromic hemolytic anemia

Question 25

How many alpha thalassemia genes are deleted in Hb Bart?

Answer 25

All 4

Question 26

How many alpha thalassemia genes are deleted in Hb H disease?

Answer 26

3

Question 27

How many alpha thalassemia genes are deleted in alpha thalassemia minor?

Answer 27

2

Question 28

Alpha thalassemia carrier in the trans formation is more common in…

Answer 28

African descent

Question 29

Alpha thalassemia carrier in the cis formation is more common in…

Answer 29

Asian descent

Question 30

How do we test for alpha thalassemia?

Answer 30

MLPA to detect deletions and sequencing for less common point mutation

Question 31

What is characteristic of beta thalassemia?

Answer 31

Microcytic hypochromic anemia, abnormal blood smear with nucleated RBC’s, reduced hemoglobin A on analysis

Question 32

What are symptoms of someone with thalassemia major?

Answer 32

Severe anemia, hepatosplenomegaly, bone deformity

Question 33

What are symptoms of beta thalassemia intermedia?

Answer 33

Presents later in life with milder anemia and only sometimes requires transfusion. They are at risk for iron overload via the diet due to ineffective erythropoiesis

Question 34

What is the B+ mutation?

Answer 34

Allows some beta chains to be formed but at lower rate

Question 35

What is the B0 mutation?

Answer 35

Prevents any beta chain formation

Question 36

How do we screen for beta thalassemia?

Answer 36

CBC and hemoglobin electrophoresis

Question 37

What will be low on a blood test for beta thalassemia?

Answer 37

MCV

Question 38

How can we distinguish between iron deficiency anemia and alpha thalassemia after seeing low MCV but no beta thalassemia?

Answer 38

Reflux to serum ferritin; alpha should have a normal ferritin