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CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 12: T H A L A SSE M IA /
O L IG O N U C L E O T ID E PR O B E
Summary:
A 25-year-old Mediterranean pregnant female has a history of
asymptomatic mild hypochromic, microcytic anemia, elevated hemoglobin A2
and F on electrophoresis. Her brother had severe hemolytic disease that
required transfusions and ultimately caused his premature death at age 10. She
is diagnosed with P-thalassemia minor.
Molecular genetics: Impaired production of P-globin peptide chain.
Numerous mutations have been identified in the production of
ribonucleic acid (RNA) including in the promoter region and splice
junctions.
Likely test: Oligonucleotide probe. After chorionic villus sampling is
performed, a radioactive probe can be used and hybridized with specific
genetic mutations in the fetus’ deoxyribonucleic acid (DNA), allowing
for prompt detection and prenatal diagnosis.
C L IN IC A L C O R R E L A T IO N
Anemia is the abnormally low level of hemoglobin or red blood cell mass,
which has the potential of limiting the delivery of oxygen to tissue. By far, the
most common cause of anemia is iron deficiency, leading to small volume of
red blood cells (microcytic). Another common cause of microcytic anemia is
thalassemia. Certain ethnicities have higher incidences of thalassemia, for
example, Mediterranean or East Asian descent.
This patient is of Mediterranean descent, making thalassemia more likely.
Furthermore, the microcytic (small red blood cell size) anemia in the face of
elevated hemoglobin A2 and F is consistent with P-thalassemia minor. Patients
with P-thalassemia major (Cooley anemia) typically have severe anemia
requiring frequent transfusions and shortened life expectancy. Infants will
appear healthy after birth, but as the hemoglobin F levels fall, the infant
becomes severely anemic. Females with P-thalassemia major who survive
beyond childhood are usually sterile.
A PPR O A C H TO O L IG O N U C L E O T ID E PR O B E S
O bjectives
1.
Know about the use of oligonucleotide probes for detection of muta-
tions.
2.
Know how oligonucleotide segments are synthesized.
3.
Be familiar with common mutations that cause thalassemias (substitu-
tions in TATA box, mutations in splice junction, and changes in stop
codon).
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