Hemoglobin Abnormalities in a Black Family with Hb S, Hereditary Persistence of HB F, and A γ Chain Variant; a Reevaluation Through Gene Mapping

Hemoglobin ◽  
1984 ◽  
Vol 8 (6) ◽  
pp. 549-568 ◽  
Author(s):  
T. Harano ◽  
T. H. J. Huisman
Keyword(s):  
Gene Mapping ◽  
Black Family ◽  
Hb S ◽  
Hereditary Persistence ◽  
Chain Variant

scholarly journals Hb S, Hb G-PHILADELPHIA AND α-THALASSEMIA-2 IN A BLACK FAMILY

1980 ◽  
Vol 14 (3) ◽  
pp. 266-267 ◽  
Author(s):  
A E Felice ◽  
S M Mayson ◽  
B B Webber ◽  
A Miller ◽  
M E Gravely ◽  
...  
Keyword(s):  
Black Family ◽  
Hb S

scholarly journals Hereditary persistence of fetal hemoglobin or (delta beta)o- thalassemia: three types observed in South-Chinese families

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1430-1435
Author(s):  
YT Zeng ◽  
SZ Huang ◽  
B Chen ◽  
YC Liang ◽  
ZM Chang ◽  
...  
Keyword(s):  
Gene Mapping ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Restriction Enzymes ◽  
Large Deletion ◽  
Gamma Delta ◽  
Chinese Families ◽  
Gamma Globin ◽  
Hereditary Persistence ◽  
Fetal Hemoglobin Level

Hematological and hemoglobin composition data, and results from extensive gene mapping, using a battery of restriction enzymes and probes, have been used to distinguish different types of hereditary persistence of fetal hemoglobin (HPFH) (or delta beta-thal) among three Chinese families from the southern part of China. The first (Family Z) is an A gamma-(delta beta)+-HPFH without a detectable deletion and may be the same as, or similar to, that described by Farquhar et al (Am J Hum Genet 35:611, 1983). The second (Family C) resembles a G gamma(A gamma delta beta)o-thalassemia and is characterized by a large deletion of DNA originating 3′ to the G gamma globin gene and extending beyond sequences recognized by the pRK28 probe. Data from various digests indicate possible differences in the 3c′ end of the deletion when compared with data for some other types of G gamma(A gamma delta beta)o- thalassemia, described by Trent et al (Br J Haematol 57:279, 1984). The third (Family Zh) concerns a G gamma A gamma(delta beta)+-HPFH, which is characterized in heterozygotes by a fetal hemoglobin level of 20% to 25% with a G gamma value averaging 60% and by the absence of any DNA deletion detectable by extensive gene mapping analyses. The C----G mutation at position 202 5c′ to the G gamma globin gene [characteristic for the high G gamma-(delta beta)+-HPFH (Proc Natl Acad Sci USA 81:4894, 1984; Blood 64:1292, 1984)] was absent, but the Xmn I site at position 158 5c′ to the G gamma globin gene [characteristic for a modest increase in G gamma values and thus and increased G gamma to A gamma ratio (Blood)] was present. No indication has yet been obtained explaining the elevation in both G gamma and A gamma chains; haplotyping showed that the chromosome carrying this G gamma A gamma(delta beta)+ determinant is unusual among the Chinese population.

scholarly journals The effect of alpha-thalassemia on the expression of the beta- thalassemia/HPFH heterozygote in a black family

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1132-1134 ◽  
Author(s):  
E Beutler ◽  
E Turner ◽  
W Kuhl
Keyword(s):  
Black Family ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Pedigree Analysis ◽  
Red Cells ◽  
Beta Thalassemia ◽  
Hemoglobin Gene ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Hereditary Persistence

Abstract A 2-yr-old black girl presented with a thalassemic clinical picture and was found to have nearly 100% fetal hemoglobin in her red cells. Pedigree analysis indicated that she was a heterozygote for the hereditary persistence of fetal hemoglobin gene and for a beta O- thalassemia gene. A brother, who also had nearly 100% fetal hemoglobin in his red cells, manifested, in contrast to his sister, no anemia and only minimal splenomegaly. Examination of the family's alpha-globin loci using the restriction endonuclease Eco Rl demonstrated that the brother had a single alpha-locus deletion that he had inherited from his mother. The mild clinical manifestations of this boy are consistent with the often expressed view that excess alpha chains may contribute significantly to the hematologic manifestation of beta-thalassemia.

scholarly journals Hereditary persistence of fetal hemoglobin or (delta beta)o- thalassemia: three types observed in South-Chinese families

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1430-1435 ◽  
Author(s):  
YT Zeng ◽  
SZ Huang ◽  
B Chen ◽  
YC Liang ◽  
ZM Chang ◽  
...  
Keyword(s):  
Gene Mapping ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Restriction Enzymes ◽  
Large Deletion ◽  
Gamma Delta ◽  
Chinese Families ◽  
Gamma Globin ◽  
Hereditary Persistence ◽  
Fetal Hemoglobin Level

Abstract Hematological and hemoglobin composition data, and results from extensive gene mapping, using a battery of restriction enzymes and probes, have been used to distinguish different types of hereditary persistence of fetal hemoglobin (HPFH) (or delta beta-thal) among three Chinese families from the southern part of China. The first (Family Z) is an A gamma-(delta beta)+-HPFH without a detectable deletion and may be the same as, or similar to, that described by Farquhar et al (Am J Hum Genet 35:611, 1983). The second (Family C) resembles a G gamma(A gamma delta beta)o-thalassemia and is characterized by a large deletion of DNA originating 3′ to the G gamma globin gene and extending beyond sequences recognized by the pRK28 probe. Data from various digests indicate possible differences in the 3c′ end of the deletion when compared with data for some other types of G gamma(A gamma delta beta)o- thalassemia, described by Trent et al (Br J Haematol 57:279, 1984). The third (Family Zh) concerns a G gamma A gamma(delta beta)+-HPFH, which is characterized in heterozygotes by a fetal hemoglobin level of 20% to 25% with a G gamma value averaging 60% and by the absence of any DNA deletion detectable by extensive gene mapping analyses. The C----G mutation at position 202 5c′ to the G gamma globin gene [characteristic for the high G gamma-(delta beta)+-HPFH (Proc Natl Acad Sci USA 81:4894, 1984; Blood 64:1292, 1984)] was absent, but the Xmn I site at position 158 5c′ to the G gamma globin gene [characteristic for a modest increase in G gamma values and thus and increased G gamma to A gamma ratio (Blood)] was present. No indication has yet been obtained explaining the elevation in both G gamma and A gamma chains; haplotyping showed that the chromosome carrying this G gamma A gamma(delta beta)+ determinant is unusual among the Chinese population.

scholarly journals The effect of alpha-thalassemia on the expression of the beta- thalassemia/HPFH heterozygote in a black family

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1132-1134
Author(s):  
E Beutler ◽  
E Turner ◽  
W Kuhl
Keyword(s):  
Black Family ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Pedigree Analysis ◽  
Red Cells ◽  
Beta Thalassemia ◽  
Hemoglobin Gene ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Hereditary Persistence

A 2-yr-old black girl presented with a thalassemic clinical picture and was found to have nearly 100% fetal hemoglobin in her red cells. Pedigree analysis indicated that she was a heterozygote for the hereditary persistence of fetal hemoglobin gene and for a beta O- thalassemia gene. A brother, who also had nearly 100% fetal hemoglobin in his red cells, manifested, in contrast to his sister, no anemia and only minimal splenomegaly. Examination of the family's alpha-globin loci using the restriction endonuclease Eco Rl demonstrated that the brother had a single alpha-locus deletion that he had inherited from his mother. The mild clinical manifestations of this boy are consistent with the often expressed view that excess alpha chains may contribute significantly to the hematologic manifestation of beta-thalassemia.

scholarly journals A new form of hereditary persistence of fetal hemoglobin in blacks and its association with sickle cell trait

Blood ◽  
1975 ◽  
Vol 46 (5) ◽  
pp. 683-692 ◽  
Author(s):  
G Stamatoyannopoulos ◽  
WG Wood ◽  
T Papayannopoulou ◽  
PE Nute
Keyword(s):  
Sickle Cell ◽  
Population Study ◽  
Black Family ◽  
Sickle Cell Trait ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Cell Counts ◽  
Hereditary Persistence ◽  
New Form

A new form of hereditary persistence of fetal hemoglobin (HPFH) producing 3%-8% Hb F in heterozygotes and an elevation of F-cell counts as measured by both the Kleihauer test and an antibody fluorescent procedure was found during the study of a black family. Individuals with this anomaly also had sickle cell trait. A sickle cell homozygote who had apparently inherited the HPFH determinant had 20.3% Hb F. Both types of gamma-chains were present in equal proportions in the Hb F of these individuals. A population study revealed other AS individuals with increased Hb F synthesis, three of whom were sibs. The presence of this previously unrecognized form of HPFH might explain the mild clinical manifestations and the hemoglobin phenotypes of sickle cell homozygotes with unusual elevations of Hb F.

Atypical Hemoglobin H Disease Due to Compound Heterozygosity for -α3.7 and --SEA Deletions and Heterozygosity for the β-Chain Variant Hemoglobin Raleigh (β1 VAL→ALA).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3849-3849
Author(s):  
Ferdane Kutlar ◽  
Mary Ann Knovich ◽  
Dedrey Elam ◽  
Daniel B. Jobe ◽  
David H. Buss ◽  
...  
Keyword(s):  
Globin Gene ◽  
Oxygen Affinity ◽  
Microcytic Anemia ◽  
Low Oxygen ◽  
Exertional Dyspnea ◽  
Hb S ◽  
Hb H Disease ◽  
Β Chain ◽  
Chain Variant ◽  
Hb C

Abstract The co-existence of Hemoglobin H (Hb H) disease and heterozygosity for β-chain structural variants is a rare occurrence. Hb H disease has been reported in conjunction with Hb E, Hb C, Hb S, and Hb Hamilton. The combination of Hb H disease with Hb C and Hb S reportedly results in a mild hemolytic anemia without detectable Hb H. We present a new case of atypical Hb H disease that was also heterozygous for the rare β-chain variant Hb Raleigh. The patient is a 27-year-old Cambodian female referred for the evaluation of microcytic anemia unresponsive to iron. She had a lifelong history of generalized fatigue, exertional dyspnea, and weakness in her legs. Physical exam was unremarkable except for pallor of mucuous membranes. There was no hepatosplenomegaly. She had a Hb of 9.7, HCT 30.8, MCV 56, MCH 17.6, MCHC 31.5, ferritin 92. Hb analysis on IEF revealed Hb A, Hb A2, and an abnormal band slightly more anodic to Hb A. No Hb H was observed. On cation exchange HPLC, she had 49.7% Hb A, 48.1% Hb X, and 2.2% Hb A2. Reverse phase HPLC revealed a βx chain eluting immediately before βA. Oxygen affinity was slightly reduced. PCR amplification and sequencing of the β-globin gene revealed heterozygosity for Hb Raleigh (Exon 1, codon 1, GTG→GCG, VAL→ALA). The patient was also found to be a compound heterozygote for -α3.7 and --SEA deletions. This case represents a novel interaction of a structural β-chain variant with Hb H disease. Hb Raleigh has previously been reported in Caucasians and in two Swedish families. It has decreased oxygen affinity. This is the first report of this variant in a Cambodian population. The absence of any detectable Hb H likely results from the inability of variant β-chains to form a viable tetramer with a resultant decrease in βA. The low oxygen affinity did not negatively impact on the degree of anemia. This case, like some others reported previously, shows that the accurate diagnosis of Hb H disease in association with structural β-chain variants can be established by molecular methods, and the detection of Hb H on electrophoretic and chromatographic analyses may not always be reliable.

The Occurrence of Four Globin Abnormalities in One Individual: Hb SC Disease with Hb Chicago and Deletional Alpha Thalassemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3802-3802
Author(s):  
Heather Hughes ◽  
Ferdane Kutlar ◽  
Kathleen M. McKie ◽  
Leslie Holley ◽  
Dedrey Elam ◽  
...  
Keyword(s):  
Functional Properties ◽  
Sickle Cell ◽  
Globin Gene ◽  
Crystal Formation ◽  
Local Health ◽  
Hb S ◽  
In Trans ◽  
Α Chain ◽  
Chain Variant ◽  
Hb C

Abstract The occurrence of multiple globin abnormalities in one individual is not very rare, particularly in populations where hemoglobinopathies are common. In most cases, this is of genetic interest and may pose a diagnostic challenge due to the interaction of the products of mutant α and β globin genes and the presence of hybrid hemoglobins. Co-inheritance of α globin variants with sickle cell disease (Hb SS or SC) could have an effect on the disease phenotype particularly when the variant in question has altered functional properties (decreased or increased oxygen affinity) or stability. We report a patient with Hb SC disease with co-inheritance of the α chain variant, Hb Chicago (α136Leu→Met), and deletional α thalassemia (−α3.7) in trans to the Hb Chicago mutation. The patient is a 3-year old African-American male referred to the Pediatric Sickle Cell Clinic from the local Health Department. He is the product of an uneventful term pregnancy and a normal labor. He presented with seizures at age 3 weeks and underwent a neurologic evaluation which failed to reveal any abnormality. His subsequent course was uneventful without further seizures after 1 year of age and no hospitalizations. Physical exam was unremarkable with normal growth. A CBC showed Hb of 11.3 g/dl, Hct 35.2%, MCV 64.8 fl, MCH 20.8, MCHC 32.1, RDW 18.4%, retic count of 1.7% (absolute retic count of 92,480). Cation exchange HPLC revealed a Hb F of 6.8%, A2 3.3%, Hb S 33.1% and Hb C 30.0%. Both Hb S and Hb C peaks were followed by an additional peak of 13.2% (Hb SX) and 13.6% (Hb CX) respectively suggesting the presence of an α chain variant. The total quantity of Hb S was 46.3% (Hb S+Hb SX) and that of Hb C was 43.6% (Hb C+ Hb CX), whereas Hb X amounted to 26.8%. A reversed phase HPLC confirmed the presence of an α chain variant, which eluted earlier than normal α chains; αX constituted 37.5% of the total α chains. Sequencing of the β-globin gene confirmed the presence of Hb S (GAG→GTG) and Hb C (GAG→AAG) mutations in codon 6. A PCR for α globin deletions confirmed heterozygosity for the -α3.7 deletion. α globin sequencing revealed an apparent homozygosity for a CTG→ATG (Leu→Met) substitution of the codon 136 in α2 globin gene; this “apparent” homozygosity is due to the -α3.7 deletion in trans. Family studies showed that the patient’s mother had Hb C trait with heterozygous α-thalassemia; the father was not available. The paternal grandmother had normal α-globin gene numbers, with heterozygous Hb Chicago, which was quantitated at 20.7%. Thus, the patient’s genotype was ascertained as βS/βC;-α/αChicagoα. Hb Chicago has been reported in conjunction with Hb SS but not with Hb SC disease. The co-inheritance of the α-chain variant, Hb G-Philadelphia (α68Asn→Lys) and Hb SC disease, has been reported by Lawrence et al (Blood90:2819–25, 1997); this combination resulted in the acceleration of Hb C crystal formation and decreased Hb S polymerization with a resultant mild sickling disorder. α136 is a heme contact; the Leu→Met substitution in Hb Chicago does not alter the functional properties or the stability of the molecule and is not associated with any hematologic abnormalities in heterozygous carriers. This residue is not involved in intermolecular contacts of deoxy Hb S and hence is not expected to alter the kinetics of deoxy Hb S polymerization. The significance of this observation is the accurate diagnosis of the complex Hb phenotype and ascertainment of its lack of interaction with the sickling or crystallization process.

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