Limits...
Spectrin Tunis (Sp alpha (I/78)) in a Korean family with hereditary elliptocytosis.

Han E, Kim A, Park J, Kim M, Kim Y, Han K, Kim YJ - Ann Lab Med (2013)

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, The Catholic University of Korea, Seoul, Korea. ; Catholic Genetic Laboratory Center, The Catholic University of Korea, Seoul, Korea.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Hereditary elliptocytosis (HE) is a group of disorders characterized by abnormal erythrocyte shapes that occur mainly in individuals of African and Mediterranean ancestry... Direct sequencing of the SPTA1 gene revealed a heterozygous missense mutation in exon 2, resulting in a C to T substitution at nucleotide position 121 and an amino acid change of arginine to tryptophan (c.121C>T; p.Arg41Trp) at amino acid residue 41 in the alpha l domain in both the patient and her baby (Fig. 2)... This missense mutation induces spectrin Tunis, which reduces the binding affinity for the spectrin tetramer assembly... Many SPTA1 gene mutations are single-nucleotide substitutions, whereas others are intronic mutations that cause errors in gene splicing... The location of the change within the spectrin α-chain and the homozygous or compound heterozygous status affect clinical manifestations... Remarkably, both mildly and severely affected patients are found in almost all affected kindred... Morlé et al. first described this mutation and called this disease spectrin Tunis, which causes asymptomatic HE (OMIM 130600) in patients with a heterozygous mutation... A variant was also found in a white North African man and his mother... The α variant (rs121918640) exhibits reduced binding affinity, generates an abnormal spectrin protein with an αI 78-kDa fragment, and results in a mutation, which partially destroys the ability of the dimer to form a tetramer... However, some mutations in SPTA1 are encountered more frequently than originally thought, such as the case of a mutation affecting codon α28, which contains a CpG hot spot... The CpG dinucleotide has also been implicated in a number of band 3 gene hot spots, most of which encode arginine (CGN, N indicating any nucleotide)... The mutation resulting in spectrin Tunis occurs in the CpG dinucleotide at codon 41, which also encodes arginine (CGG)... The patient who transmits the production-defective spectrin allele is clinically normal with unremarkable erythrocyte morphology because α-spectrin is normally synthesized in a 2- to 3-fold excess, and the output from a single normal α-spectrin allele is sufficient to maintain membrane integrity... Because this α-spectrin variant is related to asymptomatic HE in a heterozygous state, the outcomes may include mild elliptocytosis in the proband and her baby.

Show MeSH

Related in: MedlinePlus

(A) Marked anisopoikilocytosis, including elliptocytosis, schistocytes, and teardrop cells, on a peripheral blood smear. (B) Bone marrow aspirates showing hypercellularity and erythroid hyperplasia (Wright-Giemsa Stain, ×1,000).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3756249&req=5

Figure 1: (A) Marked anisopoikilocytosis, including elliptocytosis, schistocytes, and teardrop cells, on a peripheral blood smear. (B) Bone marrow aspirates showing hypercellularity and erythroid hyperplasia (Wright-Giemsa Stain, ×1,000).

Mentions: We studied a Korean family presenting with HE. To our knowledge, this is the first report to describe a family of Korean descent diagnosed with HE by molecular analysis. A 28-yr-old woman visited our hospital and was found to have anemia during a routine health screening. She did not complain of symptoms related to anemia. Abdominal ultrasonography revealed splenomegaly (craniocaudal length, 13.8 cm). Marked anisopoikilocytosis, including elliptocytes, schistocytes, and teardrop cells, were detected on a peripheral blood smear (Fig. 1A). A complete blood count revealed pancytopenia (white blood cell count, 3.88×109/L; hemoglobin level, 7.6 g/dL; and platelet count, 95×109/L). Red cell indices revealed macrocytic normochromic anemia (red blood cell count, 2.20×1012/L; reticulocyte count, 0.968×1012/L; hematocrit value, 24%; mean corpuscular volume, 109.1 fL; and mean corpuscular hemoglobin concentration, 31.7%). We ruled out iron deficiency or megaloblastic anemia based on the following laboratory findings: serum iron level, 96 µg/dL (reference range: 50-150 µg/dL); ferritin level, 104 ng/mL (10-120 ng/mL); total iron-binding capacity, 204 µg/dL (250-450 µg/dL); vitamin B12 concentration, >1,500 pg/mL (180-914 pg/mL); and folate concentration, 7.47 ng/mL (3.1-19.9 ng/mL). The serum concentrations of total bilirubin (1.02 mg/dL), haptoglobin (<30 mg/dL), and lactate dehydrogenase (556 U/L) confirmed the presence of a hemolytic process. Bone marrow studies showed hypercellularity and erythroid hyperplasia with G:E ratio of 0.67:1 (Fig. 1B), and cytogenetic studies revealed a normal karyotype (46,XX[20]).


Spectrin Tunis (Sp alpha (I/78)) in a Korean family with hereditary elliptocytosis.

Han E, Kim A, Park J, Kim M, Kim Y, Han K, Kim YJ - Ann Lab Med (2013)

(A) Marked anisopoikilocytosis, including elliptocytosis, schistocytes, and teardrop cells, on a peripheral blood smear. (B) Bone marrow aspirates showing hypercellularity and erythroid hyperplasia (Wright-Giemsa Stain, ×1,000).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756249&req=5

Figure 1: (A) Marked anisopoikilocytosis, including elliptocytosis, schistocytes, and teardrop cells, on a peripheral blood smear. (B) Bone marrow aspirates showing hypercellularity and erythroid hyperplasia (Wright-Giemsa Stain, ×1,000).
Mentions: We studied a Korean family presenting with HE. To our knowledge, this is the first report to describe a family of Korean descent diagnosed with HE by molecular analysis. A 28-yr-old woman visited our hospital and was found to have anemia during a routine health screening. She did not complain of symptoms related to anemia. Abdominal ultrasonography revealed splenomegaly (craniocaudal length, 13.8 cm). Marked anisopoikilocytosis, including elliptocytes, schistocytes, and teardrop cells, were detected on a peripheral blood smear (Fig. 1A). A complete blood count revealed pancytopenia (white blood cell count, 3.88×109/L; hemoglobin level, 7.6 g/dL; and platelet count, 95×109/L). Red cell indices revealed macrocytic normochromic anemia (red blood cell count, 2.20×1012/L; reticulocyte count, 0.968×1012/L; hematocrit value, 24%; mean corpuscular volume, 109.1 fL; and mean corpuscular hemoglobin concentration, 31.7%). We ruled out iron deficiency or megaloblastic anemia based on the following laboratory findings: serum iron level, 96 µg/dL (reference range: 50-150 µg/dL); ferritin level, 104 ng/mL (10-120 ng/mL); total iron-binding capacity, 204 µg/dL (250-450 µg/dL); vitamin B12 concentration, >1,500 pg/mL (180-914 pg/mL); and folate concentration, 7.47 ng/mL (3.1-19.9 ng/mL). The serum concentrations of total bilirubin (1.02 mg/dL), haptoglobin (<30 mg/dL), and lactate dehydrogenase (556 U/L) confirmed the presence of a hemolytic process. Bone marrow studies showed hypercellularity and erythroid hyperplasia with G:E ratio of 0.67:1 (Fig. 1B), and cytogenetic studies revealed a normal karyotype (46,XX[20]).

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, The Catholic University of Korea, Seoul, Korea. ; Catholic Genetic Laboratory Center, The Catholic University of Korea, Seoul, Korea.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Hereditary elliptocytosis (HE) is a group of disorders characterized by abnormal erythrocyte shapes that occur mainly in individuals of African and Mediterranean ancestry... Direct sequencing of the SPTA1 gene revealed a heterozygous missense mutation in exon 2, resulting in a C to T substitution at nucleotide position 121 and an amino acid change of arginine to tryptophan (c.121C>T; p.Arg41Trp) at amino acid residue 41 in the alpha l domain in both the patient and her baby (Fig. 2)... This missense mutation induces spectrin Tunis, which reduces the binding affinity for the spectrin tetramer assembly... Many SPTA1 gene mutations are single-nucleotide substitutions, whereas others are intronic mutations that cause errors in gene splicing... The location of the change within the spectrin α-chain and the homozygous or compound heterozygous status affect clinical manifestations... Remarkably, both mildly and severely affected patients are found in almost all affected kindred... Morlé et al. first described this mutation and called this disease spectrin Tunis, which causes asymptomatic HE (OMIM 130600) in patients with a heterozygous mutation... A variant was also found in a white North African man and his mother... The α variant (rs121918640) exhibits reduced binding affinity, generates an abnormal spectrin protein with an αI 78-kDa fragment, and results in a mutation, which partially destroys the ability of the dimer to form a tetramer... However, some mutations in SPTA1 are encountered more frequently than originally thought, such as the case of a mutation affecting codon α28, which contains a CpG hot spot... The CpG dinucleotide has also been implicated in a number of band 3 gene hot spots, most of which encode arginine (CGN, N indicating any nucleotide)... The mutation resulting in spectrin Tunis occurs in the CpG dinucleotide at codon 41, which also encodes arginine (CGG)... The patient who transmits the production-defective spectrin allele is clinically normal with unremarkable erythrocyte morphology because α-spectrin is normally synthesized in a 2- to 3-fold excess, and the output from a single normal α-spectrin allele is sufficient to maintain membrane integrity... Because this α-spectrin variant is related to asymptomatic HE in a heterozygous state, the outcomes may include mild elliptocytosis in the proband and her baby.

Show MeSH
Related in: MedlinePlus