Exome-Based Trio Analysis for Diagnosis of the Cause of Congenital Severe Hemolytic Anemia in a Child
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Exome-Based Trio Analysis for Diagnosis of the Cause of Congenital Severe Hemolytic Anemia in a Child. / Rieneck, Klaus; Lausen, Birgitte; Clausen, Frederik Banch; Jønson, Lars; Hansen, Anne Todsen; Dziegiel, Morten Hanefeld.
In: Transfusion Medicine and Hemotherapy, Vol. 49, No. 5, 2022, p. 320-325.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Exome-Based Trio Analysis for Diagnosis of the Cause of Congenital Severe Hemolytic Anemia in a Child
AU - Rieneck, Klaus
AU - Lausen, Birgitte
AU - Clausen, Frederik Banch
AU - Jønson, Lars
AU - Hansen, Anne Todsen
AU - Dziegiel, Morten Hanefeld
N1 - Publisher Copyright: © 2022 The Author(s). Published by S. Karger AG, Basel.
PY - 2022
Y1 - 2022
N2 - Inborn hemolytic anemia requiring frequent blood transfusions can be a life-threatening disease. Treatment, besides blood transfusion, includes iron chelation for prevention of iron accumulation due to frequent blood transfusions. We present the results of a clinical investigation where the proband was diagnosed with severe hemolytic anemia of unknown origin soon after birth. Transfusion was required every 4-6 weeks. After whole exome sequencing of the proband and his parents as well as a healthy sibling, we established that the proband had a compound heterozygous state carrying two rare variants in the erythrocytic spectrin gene, SPTA1. The maternal allele was a stop mutation (rs755630903) and the paternal allele was a missense mutation (rs375506528). The healthy sibling had the paternal variant but not the maternal variant. These rare variants of SPTA1 most likely account for the hemolytic anemia. A severely reduced osmotic resistance in the erythrocytes from the proband was demonstrated. Splenectomy considerably improved the hemolytic anemia and obviated the need for blood transfusion despite the severe clinical presentation.
AB - Inborn hemolytic anemia requiring frequent blood transfusions can be a life-threatening disease. Treatment, besides blood transfusion, includes iron chelation for prevention of iron accumulation due to frequent blood transfusions. We present the results of a clinical investigation where the proband was diagnosed with severe hemolytic anemia of unknown origin soon after birth. Transfusion was required every 4-6 weeks. After whole exome sequencing of the proband and his parents as well as a healthy sibling, we established that the proband had a compound heterozygous state carrying two rare variants in the erythrocytic spectrin gene, SPTA1. The maternal allele was a stop mutation (rs755630903) and the paternal allele was a missense mutation (rs375506528). The healthy sibling had the paternal variant but not the maternal variant. These rare variants of SPTA1 most likely account for the hemolytic anemia. A severely reduced osmotic resistance in the erythrocytes from the proband was demonstrated. Splenectomy considerably improved the hemolytic anemia and obviated the need for blood transfusion despite the severe clinical presentation.
KW - Hemolytic anemia
KW - Hereditary
KW - Spherocytosis
KW - Variant detection
KW - Whole exome sequencing
U2 - 10.1159/000523706
DO - 10.1159/000523706
M3 - Journal article
AN - SCOPUS:85128569583
VL - 49
SP - 320
EP - 325
JO - Transfusion Medicine and Hemotherapy
JF - Transfusion Medicine and Hemotherapy
SN - 1660-3796
IS - 5
ER -
ID: 314960660