scholarly journals Clinical Features and Molecular Analysis of Hb H Disease in Taiwan

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Yu-Hua Chao ◽  
Kang-Hsi Wu ◽  
Han-Ping Wu ◽  
Su-Ching Liu ◽  
Ching-Tien Peng ◽  
...  
Keyword(s):  
Clinical Features ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Clinical Severity ◽  
Blood Transfusions ◽  
Limited Data ◽  
Phenotype Correlation ◽  
Younger Age ◽  
Hb H Disease ◽  
Thalassemia Mutation

Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletional Hb H disease. The (- -SEA) type ofα0-thalassemia mutation was detected in the majority of patients (>95%). The most common genotype was (- -SEA/-α3.7), followed by (- -SEA/αcsα). After further investigation of the genotype-phenotype correlation in 68 patients, we found that patients with nondeletional Hb H disease had more severe clinical features than those with deletional Hb H disease, including younger age at diagnosis, more requirement of blood transfusions, and larger proportion of patients with splenomegaly, hepatomegaly or jaundice. This is probably a consequence of the lower hemoglobin levels and the higher Hb H levels. The clinical severity was highly variable even among patients with an identical genotype, and the diversity was much more profound among patients with (- -/αcsα) genotype. Therefore, predicting the phenotype directly from the genotype in Hb H disease remains relatively difficult in Taiwan.

scholarly journals Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

scholarly journals POR polymorphisms are associated with 21 hydroxylase deficiency

2021 ◽  
Author(s):  
F. Pecori Giraldi ◽  
S. Einaudi ◽  
A. Sesta ◽  
F. Verna ◽  
M. Messina ◽  
...  
Keyword(s):  
Clinical Features ◽  
Modifier Genes ◽  
Age At Diagnosis ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Salt Wasting ◽  
Control Subjects ◽  
Younger Age ◽  
21 Hydroxylase Deficiency

Abstract Purpose Genotype–phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450  oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency Methods Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects. Results Prevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4–29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138–1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78–3.92), higher ACTH levels, and younger age at diagnosis. Conclusions Polymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

scholarly journals Anti-Fibrillarin Antibody in African American Patients with Systemic Sclerosis: Immunogenetics, Clinical Features, and Survival Analysis

2011 ◽  
Vol 38 (8) ◽  
pp. 1622-1630 ◽  
Author(s):  
ROOZBEH SHARIF ◽  
MARVIN J. FRITZLER ◽  
MAUREEN D. MAYES ◽  
EMILIO B. GONZALEZ ◽  
TERRY A. McNEARNEY ◽  
...  
Keyword(s):  
African American ◽  
Systemic Sclerosis ◽  
Clinical Features ◽  
Age Of Onset ◽  
Strong Association ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Cox Proportional Hazards ◽  
Digital Ulcers ◽  
Younger Age

Objective.Anti-U3-RNP, or anti-fibrillarin antibodies (AFA), are detected more frequently among African American (AA) patients with systemic sclerosis (SSc) compared to other ethnic groups and are associated with distinct clinical features. We examined the immunogenetic, clinical, and survival correlates of AFA in a large group of AA patients with SSc.Methods.Overall, 278 AA patients with SSc and 328 unaffected AA controls were enrolled from 3 North American cohorts. Clinical features, autoantibody profile, and HLA class II genotyping were determined. To compare clinical manifestations, relevant clinical features were adjusted for disease duration. Cox proportional hazards regression was used to determine the effect of AFA on survival.Results.Fifty (18.5%) AA patients had AFA. After Bonferroni correction, HLA-DRB1*08:04 was associated with AFA, compared to unaffected AA controls (OR 11.5, p < 0.0001) and AFA-negative SSc patients (OR 5.2, p = 0.0002). AFA-positive AA patients had younger age of disease onset, higher frequency of digital ulcers, diarrhea, pericarditis, higher Medsger perivascular and lower Medsger lung severity indices (p = 0.004, p = 0.014, p = 0.019, p = 0.092, p = 0.006, and p = 0.016, respectively). After adjustment for age at enrollment, AFA-positive patients did not have different survival compared to patients without AFA (p = 0.493).Conclusion.Our findings demonstrate strong association between AFA and HLA-DRB1*08:04 allele in AA patients with SSc. AA SSc patients with AFA had younger age of onset, higher frequency of digital ulcers, pericarditis and severe lower gastrointestinal involvement, but less severe lung involvement compared to AA patients without AFA. Presence of AFA did not change survival.

scholarly journals Prevalence and Clinical Phenotype of the Triplicated α-Globin Genes and its Ethnic and Geographical Distribution in Guizhou of China

2020 ◽  
Author(s):  
Xi Luo ◽  
Shi-ping Chen ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Zhi-yu Peng ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background: Thalassemia is relatively epidemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype-phenotype correlation in this subpopulationMethods: A cohort of 7644 subjects was collected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results: We found that the frequency of α-globin triplication in Guizhou province was 0.759% (58/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the αααanti4.2/-α3.7 (HK αα) was 0.235% (18/7644), and the αααanti3.7/--SEA was 0.013% (1/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions: These data will be used to update the triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

Clinical Features and Morbidities of Hb H Disease in Taiwan

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4836-4836
Author(s):  
Meng Yao Lu ◽  
Ming Chung Kuo ◽  
Shih Chung Wang ◽  
Shih Hsiang Chen ◽  
Bor Sheng Ko ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Features ◽  
Serum Ferritin ◽  
Thromboembolic Event ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Globin Gene ◽  
Iron Concentration ◽  
Hb H Disease ◽  
The Mean

Abstract Introduction Patients with non-transfusion-dependent thalassemia experience a wide array of clinical complications despite their independence from frequent, regular red blood cell transfusions. They have the higher incidence of osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, cholelithiasis, thromboembolic disease, pulmonary hypertension, silent cerebral ischemia, and leg ulcers. Thalassemia is highly prevalent in Taiwan and Hb H disease is predominant. But limited data are available about clinical features and morbidities. Here, we studied clinical features and morbidities in Taiwanese patients with Hb H disease. Methods & Results We collected 90 patients with Hb H disease in three hospitals since 2014 Nov till 2016 July. Male to female were 43/59. The mean age was 33.1 years ( from 0.5 to 92.3 years). Two cases died of pulmonary hypertension and old age at 31 years old and 87 years old. Alfa-globin gene genotype studies were done in 44 cases. The (- -(SEA)) type of α(0)-thalassemia mutation was detected in all patients. Twenty- four (57.1%) cases were deletional (α(3.7)/ α(4.2)/unknown 19/4/1) and 20 (42.9%) were nondeletional (CS/RS 18/2) type. The mean of Hemoglobin (Hb) and serum ferritin level were 8.7 g/dL and 730 ng/mL. We also revealed the positive correlation between age and serum ferritin level. The liver iron concentration (LIC) were 6.694 mg Fe/g dw (n=35). The Hb, ferritin and LIC level were not different between deletional and non- deletional groups. They received the transfusion management : 1 with regular transfusion ≦ 6 weeks interval, 5 with irregular transfusion ≧ 6 weeks interval, 27 with occasional transfusion and 57 without transfusion. Fifteen cases received splenectomy. There were significantly higher prevalence for transfusion frequency and splenectomy in non-deletional group. The prevalence of morbidities were 16/79 for cholelithiasis, 12/90 for thromboembolic event, 4/90 for heart failure symptoms ( 2 for pulmonary hypertension), 5/90 for arrhythmia, 3/90 for bone fracture, 5/20 for osteoporosis and 0 for renal stone. There were non-significantly higher prevalence for morbidities in non-deletional group. Discussion & Conclusion The study provides the clinical features and the prevalence of morbidities in Hb H disease in Taiwan. Surprisingly, the prevalence of thromboembolic event and pulmonary hypertension are overlooked in our routine Hb H disease care. We need to schedule close and careful clinical follow up of Hb H patients as they get older, they get some morbidities or they are non-deletional genotype. Disclosures No relevant conflicts of interest to declare.

scholarly journals Frequency of beta S globin gene haplotypes among sickle cell patients in Nigeria

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110199
Author(s):  
Abosede Adabale ◽  
Samira Batista Lobo Makanjuola ◽  
Akinsegun Akinbami ◽  
Adedoyin Dosunmu ◽  
Alani Akanmu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Clinical Severity ◽  
Polymorphism Analysis ◽  
Cell Width ◽  
Cell Counts ◽  
Haematological Profile

Objective To determine the frequency of beta s globin gene haplotypes in Nigerian patients with sickle cell disease (SCD) and to measure their correlation with clinical and haematological characteristics. Methods This study enrolled patients with SCD and collected their peripheral blood for restriction fragment length polymorphism analysis in order to identify five polymorphic sites in the β-globin gene cluster. Results A total of 245 homozygous SCD patients (490 alleles) were included in the study. Among the analysed alleles, 426 (86.9%) had the Benin (BEN) haplotype; 19 (3.9%) had the Senegal (SEN) haplotype; 31 (6.3%) had the Cameroon haplotype; five (1.0%) had the Bantu/Central African Republic haplotype; and nine 9 (1.8%) had atypical haplotypes. No significant association was observed between the haplotypes and haematological events, although patients with the BEN/SEN haplotype showed improved red blood cell counts, haemoglobin levels and red blood cell width index. No significant association was observed between the haplotypes and the three clinical manifestations, although patients with the BEN/SEN haplotype showed a four-fold lower frequency of painful episodes. Conclusion These findings suggest that the SEN haplotype combined with the BEN haplotype might contribute toward a better haematological profile and milder clinical severity in SCD.

Hb H disease: clinical course and disease modifiers

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Suthat Fucharoen ◽  
Vip Viprakasit
Keyword(s):  
Steady State ◽  
Globin Gene ◽  
Careful Consideration ◽  
Clinical Syndrome ◽  
Clinical Severity ◽  
Globin Genes ◽  
Hemolytic Crisis ◽  
Hb H Disease ◽  
Genetic And Environmental Factors ◽  
Double Heterozygosity

Abstract Hemoglobin H (Hb H) disease is the most common form of thalassemia intermedia and has many features that require careful consideration in management. In the majority of cases, Hb H disease results from double heterozygosity for α0-thalassemia due to deletions that remove both linked α-globin genes on chromosome 16, and deletional α+-thalassemia from single α-globin gene deletions (--/−α). However, Hb H disease may occur from interactions between α0-thalassemia with non-deletional mutations (αTα or αT) or with abnormal hemoglobins such as Hb Constant Spring, Hb Paksé, Hb Quong Sze, and Hb Pak Num Po. In a steady state, patients with Hb H diseases have hemoglobin levels around 9 to 10 g/dL; however, during hemolytic crisis, which frequently develops in or after acute infections with high fever, the hemoglobin level may drop significantly and patients can develop shock or renal shutdown. Even though splenectomy leads to significant elevation of hemoglobin levels, it is not recommended because the majority of patients do well with said steady-state hemoglobin levels. Patients with non-deletional Hb H disease are usually more anemic with significant splenomegaly, and some may require regular blood transfusions and be even as severe as “Hb H hydrops fetalis.” However, there is no clear genotype-phenotype correlation associated with this severe clinical syndrome since patients with identical genotypes do not necessary show the same severity. This suggests that other genetic and environmental factors play a role in modifying the degree of clinical severity in patients with non-deletional Hb H disease.

scholarly journals Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis

2013 ◽  
Vol 39 (3) ◽  
pp. 306-316 ◽  
Author(s):  
Fernando Augusto de Lima Marson ◽  
Carmen Silvia Bertuzzo ◽  
Maria Angela Goncalves de Oliveira Ribeiro ◽  
Antonio Fernando Ribeiro ◽  
Jose Dirceu Ribeiro
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Clinical Symptoms ◽  
Pancreatic Insufficiency ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Clinical Severity ◽  
Clinical Variables ◽  
Younger Age ◽  
Severity Of The Disease

OBJECTIVE: To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. METHODS: We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. RESULTS: Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. CONCLUSIONS: The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

Significance of genetic counseling and prenatal diagnosis on α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation

2019 ◽  
Author(s):  
Zhiyang Guan ◽  
Zeyan Zhong ◽  
Hailin He ◽  
Dan Chen ◽  
Guoxing Zhong ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Globin Gene ◽  
Gene Mutations ◽  
Severe Form ◽  
Clinical Severity ◽  
Globin Genes ◽  
Significant Difference ◽  
Hb H Disease

Abstract Background : Non-deletional hemoglobin (Hb) H disease is the severest form of α- thalassemia ( thal ) compatible with post-natal life, which is caused by the interaction of an α-globin gene mutation with α 0 -thal. Therefore, it is important to identify rare α-globin gene mutations for the prevention of severe form of non-deletional Hb H disease . Methods: In all, 61,796 samples were characterized at our center. Common α- and β- thalassemia mutations were detected by routine DNA analysis (gap-PCR and PCR-RDB ). The DNA sequencing of α-globin genes was performed to identify the unknown mutation. Statistical analyses were conducted using SPSS 19.0 statistical software. Results: Of the 61,796 samples, eight were identified as α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation s, and of these, four had coinheritance with - - SEA deletion Patients with the heterozygous α2 codon 30 (-GAG) ( HBA2 : c.91_93delGAG) mutation had significantly lower levels of MCV and MCH than healthy individuals ( p < 0.01), and coinheritance with - - SEA deletion aggravated the α-thal phenotype , associated with severe Hb H disease . Moreover, a significant difference in the clinical severity was found in the Hb H disease patients with the same genotype.Conclusions: This finding is of great significance for clinicians to provide accurate genetic counseling , particularly prenatal diagnosis and establish a rigorous diagnostic procedure .

scholarly journals The Prevalence of Clinical Features in Patients with Aarskog–Scott Syndrome and Assessment of Genotype-Phenotype Correlation: A Systematic Review

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Victor Zanetti Drumond ◽  
Lucas Sousa Salgado ◽  
Camila Sousa Salgado ◽  
Vitor Augusto de Lima Oliveira ◽  
Eliene Magda de Assis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Features ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Clinical Findings ◽  
Pathogenic Variant ◽  
Genitourinary Tract ◽  
Direct Relation ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

Aarskog–Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out to analyse the prevalence of clinical manifestations found in patients, as well as to evaluate the genotype-phenotype correlation. The results obtained show that clinical findings of the craniofacial, orthopaedic, and genitourinary tract correspond to the highest scores of prevalence. The authors reclassified the primary, secondary, and additional criteria based on their prevalence. Furthermore, it was possible to observe, in accordance with previous reports, that the reported phenotypes do not present a direct relation to the underlying genotypes.

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