Molecular Diversity of Hemoglobin H Disease in India (original) (raw)

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.

Impact of h globin gene mutations on the clinical phenotype of h thalassemia in India

2004

The h thalassemias are one of the commonest group of autosomal recessive disorders in India. Although majority of patients are severe and transfusion-dependent, about 10–15% of cases have a milder phenotype. We evaluated the role of h gene mutations in modulating the clinical presentation of 342 h thalassemia patients which included 278 severe thalassemia major (TM) and 64 thalassemia intermedia (TI) cases (severe TI: 27; mild TI: 37) from this region. Thirteen h thalassemia mutations were characterized by reverse dot blot hybridization or amplification refractory mutation system (ARMS); denaturing gradient gel electrophoresis (DGGE) analysis and DNA sequencing helped to characterize the remaining nine mutations. Majority of the patients in the thalassemia major and thalassemia intermedia groups had severe h or h mutations. IVS 1-5 (GYC) was the commonest mutation in the three groups. The six severe and common Indian mutations [(IVS 1-5 (GYC), 619 bp deletion, IVS 1-1 (GYT), codons ...

Molecular Heterogeneity of Hb H Disease in India

Thalassemia Reports

Alpha thalassemia is an autosomal recessive disorder caused by large deletions and/or point mutations in the α- globin genes. Hemoglobin H (Hb H) disease is most frequently due to deletion of three of the four α globin genes associated with variable clinical severity depending on the genotype. There are few reports on Hb H disease in Indians where genotyping has been done and we have reviewed the molecular and clinical heterogeneity of these cases. An electronic search for relevant articles was conducted using two journal databases, i.e., PubMed and Science Direct using the key words “Hb H Disease”, “Hemoglobin H”, “α-thalassemia”, “mutations”, “molecular heterogeneity”, “case reports” and “India”. This review was performed based on preferred reporting items for the systematic review and meta-analysis protocols (PRISMA-P) guidelines. The molecular spectrum of Hb H disease in Indians includes the most common [-α3.7, -α4.2, --SA, Poly A (AATAAA→AATA--), Hb Sallanches], rare [--SEA, --...

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.

Hemoglobin H (Hb H) disease in Canada: Molecular diagnosis and review of 116 cases

American Journal of Hematology, 2001

Over the past decade, we have characterized at the DNA level a total of 116 hemoglobin H (Hb H) disease patients living in Canada. The majority of patients were of southeast Asian descent (Chinese, Filipino, Laotian, Vietnamese), with a small number being of Mediterranean, Middle Eastern or East Indian background. A total of 15 distinct genotypes were detected, all but one being compound heterozygotes for a two-gene cis deletion and a single-gene deletion (-␣/−) or a non-deletion mutation of the ␣2-globin gene (␣ T ␣/−). Seven different two-gene cis deletions were encountered, along with nine singlegene deletions and point mutations. The wide range of mutations associated with Hb H disease in Canada is a reflection of the population heterogeneity. The diagnosis of Hb H disease at the molecular level is important with respect to genetic counseling and the identification of families at risk for having pregnancies affected with Hb Bart's hydrops fetalis syndrome and/or Hb H disease. Six of the Hb H disease patients in our cohort had spouses who carried single-gene deletions, making these couples at risk for having children with Hb H disease. More important, seven patients had partners who carried two-gene cis deletions. These couples are at reproductive risk for both Hb Bart's hydrops fetalis syndrome and Hb H disease. Am.

Two rare hemoglobin variants with α thalassemia in Eastern Indian population

Thalassemia Reports, 2013

The current work focuses on two rare hemoglobin (Hb) variants -Hb Grange-Blanche and Hb Hofu -found for the first time in association with α-thalassemia in Eastern India. The unusual case of Hb Grange-Blanche and FS 41/42(-CTTT) mutations in cis throws light on importance of multiple mutations and its coinheritance with ααα anti3.7 triplication indicates a possible cause for the clinical severity in β-thalassemia carriers.