Atypical hemoglobin H disease in a Thai patient resulting from a combination of alpha-thalassemia 1 and hemoglobin Constant Spring with hemoglobin J Bangkok heterozygosity (original) (raw)
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Molecular Diversity of Hemoglobin H Disease in India: Table 1
American Journal of Clinical Pathology, 2010
This study was undertaken to evaluate the variable clinical expression of hemoglobin (Hb) H disease in India. For the study, α genotyping was done in 8 patients with Hb H disease using multiplex polymerase chain reaction and DNA sequencing. The study revealed that 4 genotypes (-SEA /-α 3.7 ,-SA /-α 3.7 ,-SEA /-α 3.7 Sallanches ,-α 3.7 /-α 3.7 Sallanches) were responsible for Hb H disease, the α+ thalassemia mutation (-α 3.7 deletion) being the most common defect. The nondeletional mutation Hb Sallanches (α 2 codon 104 G → A) was seen in 3 cases. Two unique and novel genotypes leading to Hb H disease were characterized (-SEA /-α 3.7 Sallanches and-α 3.7 /-α 3.7 Sallanches). Because a majority of patients with Hb H disease do not have severe manifestations, prenatal diagnosis is usually unwarranted in India.
Molecular Diversity of Hemoglobin H Disease in India
American Journal of Clinical Pathology, 2010
This study was undertaken to evaluate the variable clinical expression of hemoglobin (Hb) H disease in India. For the study, alpha genotyping was done in 8 patients with Hb H disease using multiplex polymerase chain reaction and DNA sequencing. The study revealed that 4 genotypes (- -(SEA)/ -alpha(3.7), - -(SA)/-alpha(3.7), - -(SEA)/-alpha(3.7 Sallanches), - -alpha(3.7)/-alpha(3.7 Sallanches)) were responsible for Hb H disease, the alpha+ thalassemia mutation (-alpha(3.7) deletion) being the most common defect. The nondeletional mutation Hb Sallanches (alpha 2 codon 104 G --> A) was seen in 3 cases. Two unique and novel genotypes leading to Hb H disease were characterized (- -(SEA)/-alpha(3.7 Sallanches) and -alpha(3.7)/-alpha(3.7 Sallanches)). Because a majority of patients with Hb H disease do not have severe manifestations, prenatal diagnosis is usually unwarranted in India.
Phenotype-genotype correlation in haemoglobin H disease in childhood
Journal of Medical Genetics, 1983
In this study we used restriction endonuclease mapping to characterise the molecular defect responsible for haemoglobin H disease in 14 Sardinian children. The resulting genotypes were then correlated with the respective clinical and haematological phenotypes. We found that patients with the combination of non-deletion xc+-thalassaemia [(oc)th] and deletion cx°-thalassaemia (-Med) have a more severe phenotype than that resulting from the interaction of deletion Occthalassaemia (__Med) and a+-thalassaemia (-oc) determinants. Clinically, presentation was earlier and with moderate anaemia or haemolytic crisis, enlargement of the liver and spleen, and thalassaemic bone changes. Haematologically, the anaemia was more severe and there were higher bilirubin levels, reticulocyte counts, Hb H levels, and percentage of red blood cells with inclusion bodies. These results suggest that in those Hb H disease patients with the non-deletion [(ccc)th] determinant, two a globin genes produce fewer oc globin chains than a single cx globin locus. The two x globin structural genes lie on chromosome 16 linked to one g globin gene, a ¢-like gene (N.i), and an alike pseudogene (y cx,) in the order 5'-(2p 3'i 2 Several different lesions of this gene complex produce the cx-thalassaemias, a group of genetic disorders characterised by a reduced or absent output of oc globin chains within the red blood cells. Haemoglobin H (Hb H) disease, the most important clinical form of oc-thalassaemia, is a hereditary microcytic anaemia most frequently found in South Asian and Mediterranean populations.3 Most commonly, this disorder results from the interaction of a deletion form of ac°-thalassaemia (-) with a deletion c+-thalassaemia (-a) determinant.4-6 However, this condition can also be produced either by the combination of a deletion form of cc°-thalassaemia (-) with a non-deletion oc+-thalassaemia determinant [(CXCX)th]6-9 or by the homozygous state of a non-deletion defect [(aCC)th/(ac)th], so far seen only in Saudi Arabs.'0 The cx°-thalassaemia determinant, characterised by a complete suppression of cc globin chain production, includes haplotypes with loss of both cx globin structural loci as well as haplotypes with residual but non-functional cx globin genes.6 11-13 *On leave fronm the
PLoS ONE, 2014
Background: Hemoglobin (Hb) variants are structurally inherited changes of globin chains. Accurate diagnoses of these variants are important for planning of appropriate management and genetic counseling. Since no epidemiological study has been conducted before, we have investigated frequencies, molecular and hematological features of Hb variants found in a large cohort of Thai subjects. Materials and Methods: Study was conducted on 26,013 unrelated subjects, inhabiting in all geographical parts of Thailand over a period of 11 years from January 2002-December 2012. Hb analysis was done on high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). Mutations causing Hb variants were identified using PCR and related techniques. Results: Among 26,013 subjects investigated, 636 (2.4%) were found to carry Hb variants. Of these 636 subjects, 142 (22.4%) carried a-chain variants with 13 different mutations. The remaining included 451 (70.9%) cases with 16 b-chain variants, 37 (5.8%) cases with Hb Lepore (db-hybrid Hb) and 6 (0.9%) cases with a single d-chain variant. The most common a-globin chain variant was the Hb Q-Thailand (a 74GAC-CAC, Asp-His) which was found in 101 cases (15.8%). For b-globin chain variants, Hb Hope (b 136GGT-GAT, Gly-Asp) and Hb Tak (b 146+AC, Ter-Thr) are the two most common ones, found in 121 (19.0%) and 90 (14.2%) cases, respectively. Seven Hb variants have never been found in Thai population. Hb analysis profiles on HPLC or CE of these variants were illustrated to guide presumptive diagnostics. Conclusions: Hb variants are common and heterogeneous in Thai population. With varieties of thalassemias and hemoglobinopathies in the population, interactions between them leading to complex syndromes are common and render their diagnoses difficult in routine practices. Knowledge of the spectrum, molecular basis, genotype-phenotype correlation and diagnostic features should prove useful for prevention and control of the diseases in the region.
Clinical and genetic characteristics of hemoglobin H disease in Iran.
Pediatric Hematology and Oncology, 2021
Hemoglobin H (Hb H) disease is a subtype of α-thalassemia caused by deletional and/or non-deletional mutations in three alpha-globin genes in which the various genotypes determine the disease severity. This study was aimed to investigate the frequency of alpha gene mutations and genotypes and their correlation with hematological and clinical characteristics in Iran. Among 202 patients diagnosed with Hb H disease through a national study in Iran according to standard methods, we had access to the hematologic and clinical findings and genetic data of 101 patients in whom genetic study was performed. Genomic DNA from peripheral blood was extracted and analyzed for identification of α-globin gene mutations using Multiplex Gap Polymerase Chain Reaction, Reverse Hybridization Assay, and finally Direct DNA Sequencing method. Twenty-one different mutations and thirty genotypes were detected in 101 patients with Hb H disease. In total, 39 patients (38.6%) were deletional and 62 patients (61.4%) were non-deletional type of the disease. The -- MED mutation was highly prevalent in almost half of the patients (56.4%). Among various genotypes, –MED/-a3.7 (29.7%) and -α20.5/-α5NT (6.9%) were the most prevalent genotypes found in the studied group. Patients with non-deletional type presented with more severe hematological and clinical findings. Hb H percentage and serum ferritin levels were significantly higher in non-deletional patients in comparison to the deletional group (p<0.05). 12 (11.9%) and 40 (39.6%) out of 101 patients were on regular and occasional transfusions, respectively. 83% of those with regular transfusion belonged to the non-deletional group. Among transfusion-dependent patients, –MED/ αCSα and α20.5/-α5NT were the most common genotypes. In this study, two patients with -α20.5/αCSα and –MED/α−5NT genotypes experienced thrombotic events. This study indicated that although non-deletional genotypes of Hb H disease were responsible for more clinical severity of the disease, due to the presence of severe phenotypes even in deletional types, no definite correlation was found between genotype and phenotype.
Molecular and hematological profiles of hemoglobin EE disease with different forms of a-thalassemia
Ann Hematol, 2006
We describe hematologic and DNA characterization of hemoglobin (Hb) E homozygote with various forms of α-thalassemia in Thai individuals. Altogether, 131 unrelated adult subjects with Hb EE at routine Hb analysis were studied. Forty-two cases were found to carry α-thalassemia with ten different genotypes. These included 21 cases with α +-thalassemia heterozygote (-α 3.7 /αα), one case with α +-thalassemia heterozygote (-α 4.2 /αα), six cases with Hb Constant Spring heterozygote (α CS α/αα), four cases with homozygous α +thalassemia (-α 3.7 /-α 3.7), one case with homozygous α +-thalassemia (-α 4.2 /-α 4.2), two cases with compound α +-thalassemia/Hb Constant Spring (-α 3.7 /α CS α), one case with compound α +-thalassemia/Hb Paksé (-α 3.7 /α PS α), four cases with α 0-thalassemia heterozygote (-SEA /αα), and, unexpectedly, two cases with compound α 0-thalassemia/α +-thalassemia [(-SEA /-α 3.7) and (-SEA /-α 4.2)]. The hematological expression of these Hb E homozygotes with various forms of αthalassemia was presented comparatively with those of the 89 cases of pure Hb E homozygotes. Overlapping levels of Hb E, Hb F, and other hematological parameters were observed which did not predict clinical severity, indicating a need for α-globin gene analysis for accurate diagnosis and improved genetic counseling.
Annals of Hematology, 2007
We report on a Thai female patient who presented with hypochromic microcytic anemia, hepatosplenomegaly, and failure to thrive since 3 years of age. Hematological and hemoglobin (Hb) analysis were consistent with a clinical diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been detected. During the 20 years of follow-up, this patient experienced several episodes of hemolytic crisis, which worsened her anemia, necessitating blood transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable globin gene mutation affecting codon 125 (CTG→CCG) of α 2 globin gene in trans with the commonest α 0 thalassemia (-SEA ) in the patient. This report highlights the clinical significance of Hb QS in Southeast Asians, as previously almost all of the patients described with this variant were of Chinese origin.