Identification of a new β-thalassaemia variant Term CD+32(HBB: c.32A>C) in two Chinese families

2020 ◽  
Vol 73 (9) ◽  
pp. 593-596
Author(s):  
Jianlong Zhuang ◽  
Yu Zheng ◽  
Yuanbai Wang ◽  
Qianmei Zhuang ◽  
Yuying Jiang ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Elevated Level ◽  
Globin Gene ◽  
Novel Mutations ◽  
Fujian Province ◽  
Chinese Families ◽  
Rare Mutation ◽  
Direct Dna Sequencing ◽  
Her Family ◽  
Blood Disorder

Aimsβ-Thalassaemia is an inherited blood disorder caused by mutations in the β-globin gene cluster. Molecular characterisation of β-thalassaemia is essential for its diagnosis and management. More and more rare and novel mutations have been reported.MethodsTwo Chinese families with β-thalassaemia from Fujian Province were recruited in this study. The phenotypes of the probands were confirmed through haematological analysis. Routine molecular analysis of thalassaemia was employed to identify the common mutations of thalassaemia. The rare and novel mutations were detected by direct DNA sequencing.ResultsIn family 1, the proband, a Chinese woman aged 31 years, showed elevated level of haemoglobin A2 (HbA2). No common mutations associated with β-thalassaemia were detected, whereas a rare mutation Term CD+32(HBB: c.32A>C) was identified through DNA sequencing. Subsequent investigation of the β-thalassaemia mutation in her family showed that her mother, her brother as well as her nephew also carried this mutation. In addition, both the proband’s husband and her son carrying the rare --THAI mutation exhibited decreased levels of MCH, MCH and HbA2. In family 2, the proband, a child aged 1 year, showed elevated level of HbA2, but had no common mutations of β-thalassaemia. The proband was identified carrying the mutation Term CD+32(HBB: c.32A>C), which was inherited from his mother.ConclusionsIn this study, we first report a rare β-thalassaemia mutation in Fujian Province, Southeast China. Moreover, our study also identified this rare mutation in humans. This finding has helped broaden the spectrum of β-thalassaemia mutations in our region and suggested that this rare mutation may be more prevalent in the Chinese population.

scholarly journals SPECTRUM OF BETA GLOBIN GENE MUTATIONS IN EGYPTIAN CHILDREN WITH β- THALASSEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014071 ◽  
Author(s):  
MR El-Shanshory ◽  
Adel Abd Elhaleim Hagag
Keyword(s):  
Dna Sequencing ◽  
Blood Count ◽  
Complete Blood Count ◽  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Direct Dna Sequencing ◽  
Rare Mutations ◽  
Egyptian Children

Background: The molecular defects resulting in β-thalassemia phenotype, in the Egyptian population show a clear heterogenic mutations pattern. PCR based techniques, including direct DNA sequencing are effective on the molecular detection and characterization of these mutations. The molecular characterization of β-thalassemia is absolutely necessary for carrier screening, for genetic counseling, and to offer prenatal diagnosis.The aim of the work: was to evaluate the different β-globin gene mutations in one hundred Egyptian children with β-thalassemia. Patients and Methods: One hundred of β-thalassemic Egyptian children, covering most Egyptian Governorates. All patients were subjected to meticulous history taking, clinical examinations, complete blood count, complete blood count, hemoglobin electrophoresis, serum ferritin and direct fluorescent DNA sequencing of β-globin gene to detect the frequency of different mutations in studied patients. Results: The most common mutations among patients were IVS I-110(G>A) 48%, IVS I-6(T>C) 40%, IVS I-1(G>A)19%,IVS I-5(G>C)10%, IVS II-848 (C>A) 9%, IVS II-745(C>G) 8%, IVS II-1(G>A) 7%, codon"Cd"39(C> T) 4%,-87(C>G) 3% and the rare mutations were: Cd37 (G>A), Cd8 (-AA), Cd29(-G), Cd5 (-CT), Cd6(-A), Cd8/9(+G), Cd 106/107(+G), Cd27(C>T), IVS II-16(G> C), Cd 28 (-C), Cap+1(A>C), -88(C>A), all of these rare mutations were present in 1%. There was considerable variation in phenotypic severity among patients resulting from interaction of different β° and β+mutations, 79(79%) patients were thalassemia major (TM) and 21(21%) were thassemia intermedia (TI), without genotype phenotype association. Conclusion: Direct DNA sequencing provides insights for the frequency of different mutations in β- thalassemic patients including rare and /or unknown ones.

scholarly journals Complex Interaction of Hb Q-Thailand with α and β Thalassemia in a Hakka Family

2020 ◽  
Author(s):  
Lin Zheng ◽  
Hailong Huang ◽  
Xiaoqing Wu ◽  
Qingmei Shen ◽  
Meihuan Chen ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Hematological Parameters ◽  
Globin Gene ◽  
Family Members ◽  
Migration Time ◽  
Fujian Province ◽  
Her Family ◽  
Microcytic Hypochromic Anaemia ◽  
Haemoglobin Disorders ◽  
Abnormal Band

Abstract Background HbQ-Thailand is an α-globin chain variant that results from a point mutation at codon 74 of the α1-globin gene on chromosome 16p. It commonly appears with a leftward single α-globin gene deletion (-α 4.2 ). There have been few reports regarding the interaction between HbQ-Thailand and other globin gene disorders. Here we found and diagnosed it in the Hakka population of the Fujian Province, China. The study provides an important reference for the clinic diagnose and genetic counseling of thalassemia and hemoglobin diseases. Methods Fresh peripheral blood samples were collected from the proband and her family members testing hematological parameters, hemoglobin components, thalassemia gene, and hemoglobin variants. Results The proband (II1) and her sister (II5) manifested in the obvious microcytic hypochromic anaemia. The CE electropherogram of II1 showed an abnormal band in the migration time at 185 s, which was confirmed as HbQ-Thailand. Another exception band appeared at 250 s of migration time and was proved to be HbE by sequence analysis method. The CE electropherogram of I1 and II3 showed an anomalous band HbE. The mother of the proband (I2) and the III4 and III5 of the family members showed a HbQ-Thailand. The gene results showed that the father (I1) also carried α- and β-thalassemia genes. His genotype was -- SEA and β codons26 ; -- SEA was inherited to II1, II 3, II5, III 1, and III2, and β codons26 was inherited to II1 and II3. The mother (I2) carries the -α 4.2 gene, which was inherited to II1, II5, III4, and III5. Conclusion It was complex to diagnose when the thalassemia combined with several abnormal haemoglobin disorders, and we may use various methods to mutual confirmation. Here we found and diagnosed a rare hemoglobin disease in the Hakka population of the Fujian Province. The study provides an important reference for the clinic diagnose and genetic counseling.

Surveyor™ Nuclease: A New Rapid and Effective Strategy for Detection of Single Nucleotide Changes in Alpha Globin Genes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3653-3653
Author(s):  
Mammen Chandy ◽  
Eunice E. Sindhuvi ◽  
R.V. Shaji ◽  
Vikram Mathews ◽  
Biju George ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Point Mutation ◽  
Globin Gene ◽  
Point Mutations ◽  
Screening Methods ◽  
Compound Heterozygous ◽  
Globin Genes ◽  
Direct Dna Sequencing ◽  
Alpha Thalassemia ◽  
Alpha Globin

Abstract Alpha thalassemia is the most common globin gene disorder in the world and the disease is caused by mutations in either the alpha2 or alpha1 genes. Deletions of one (-α) or both (--) of these genes are the most common cause of alpha-thalassemia, while point mutations and small insertions/deletions are present but at a much lower frequency (5%). The number of point mutations described in these genes has been steadily increasing, with greater than 40 identified to date. Identifying these point mutations acquires importance as patients with non-deletional hemoglobin (Hb) H disease are more severely affected. Comprehensive evaluation of α globin genes is also essential while determining the molecular basis of the thalassemia intermedia phenotype. Mutations in the alpha globin gene can be detected either by direct DNA sequencing or by screening methods. Although small (about 1kb, 3 exons and 2 introns), the alpha-globin genes are duplicate and highly G-C rich, which makes them difficult to denature and therefore reducing sequencing efficiency and causing frequent artifacts. We have developed a simple and robust method based on mismatch-specific DNA endonuclease, SurveyorTM Nuclease. Genomic DNA control samples (n=21) harboring 12 different nucleotide changes characterized by direct DNA sequencing in either the alpha2 or alpha1 samples were used to validate this method. These samples were heterozygous or homozygous for each point mutation, or compound heterozygous for a deletion and the point mutation. Controls were amplified by gene specific primers designed by Primer3 software followed by digestion with SurveyorTM Nuclease. This endonuclease is a member of the CEL nuclease family of mismatch-specific nucleases derived from celery. It recognizes all insertions, deletions and base substitutions, and cleaves the mismatch of any heteroduplex DNA. After digestion, cleavage products are analyzed by agarose gel electrophoresis. The size of the digestion products indicates the location of the mutation, which is then confirmed and characterized by sequencing. All the 12 different nucleotide changes [α1 CD 14 TàC, α2 CD 104 TàG, α2 IVS II-55 TàG, α1 IVS II 141 TàC, α1 IVS I 117 GàT, α2 IVS I 1 GàA, Poly A (-AA), α1 CD 119 CàT, α2 IVS I 116, α2 CD 22 CàT, α2 CD 29 TàC, α2 +15 CàG] in the alpha globin genes were detected by this assay indicating a high sensitivity and specificity of this method. Mutation screening by SurveyorTM Nuclease is rapid (~ 5 hours), cost effective ($8/sample) and sensitive (100%). This assay in combination with the multiplex-PCR for screening the common alpha globin gene deletions will be the most comprehensive and economical approach for genetic diagnosis of alpha thalassaemia. Mismatch specific nucleases may have increasing application as a mutation detection strategy for human genetic diseases.

scholarly journals Fannin-Lubbock-I [α2β2119(GLY>ASP)], a rare mutation in the beta-globin gene, has been detected for the first time in a Hindu Brahmin family in West Bengal, India

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Jayasri Basak ◽  
Deboshree Bhattacharyya ◽  
Ashis Mukhopadhyay
Keyword(s):  
Amino Acid ◽  
West Bengal ◽  
Globin Gene ◽  
Beta Globin ◽  
Globin Chain ◽  
Rare Mutation ◽  
Direct Dna Sequencing ◽  
Beta Globin Gene ◽  
First Time ◽  
Amino Acid Glycine

AbstractThis study aims to describe the hemoglobin Fannin-Lubbock-I, which has a rare mutation substituting the amino acid glycine with aspartic acid at codon 119 of the β-globin chain. A Bengalee Hindu Brahmin family from Kolkata in West Bengal was the focus of this study. Molecular analysis using ARMS-PCR and direct DNA sequencing revealed the presence of a GGC > GAC mutation in codon 119 of the β-globin gene in a heterozygote state in three women of the same family. This is the first report of the hemoglobin Fannin-Lubbock-I from India. Our results will help to identify this mutation, which is relatively infrequent in our population.

scholarly journals Detection of a Possible Bioterrorism Agent, Francisella sp., in a Clinical Specimen by Use of Next-Generation Direct DNA Sequencing

2012 ◽  
Vol 50 (5) ◽  
pp. 1810-1812 ◽  
Author(s):  
M. Kuroda ◽  
T. Sekizuka ◽  
F. Shinya ◽  
F. Takeuchi ◽  
T. Kanno ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Clinical Specimen ◽  
Next Generation ◽  
Direct Dna Sequencing ◽  
Bioterrorism Agent

scholarly journals Analysis of Crohn’s Disease-Related CARD15 Polymorphisms in Spanish Patients with Idiopathic Uveitis

2008 ◽  
Vol 24 (2) ◽  
pp. 111-117 ◽  
Author(s):  
N. Rodríguez-Pérez ◽  
A. Aguinaga-Barrilero ◽  
Marina B. Gorroño-Echebarría ◽  
Mercedes Pérez-Blas ◽  
J. M. Martín-Villa
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dna Sequencing ◽  
Healthy Subjects ◽  
Gene Frequency ◽  
Spanish Population ◽  
Control Group ◽  
Accession Number ◽  
Direct Dna Sequencing ◽  
Exon 11

We wished to analyse the frequency of Crohn’s disease-linked CARD15 polymorphisms (P268S, R702W, G908R and 1007fs) in a group of Spanish patients with idiopathic uveitis. To this aim, DNA samples were obtained from 111 unrelated patients. P268S, R702W and G908R polymorphisms were detected using TaqMan Genotyping kits (Applied Biosystems), and the 1007fs variation by direct DNA sequencing. Control group consisted of 105 healthy subjects.None of the polymorphisms studied revealed a significant increase in the groups of patients, when compared to the control group. Thus, P268S is found in 50% of patients (gene frequency 0.284) vs 44% of control individuals (gene frequency 0.245); R702W in 7% of patients (0.036) vs 7% (0.033); G908R in 2% of patients (0.009) vs 4% (0.019) and, finally, 1007fsin 2% of uveitis patients (0.008) vs 4% (0.021). Moreover, DNA sequencing has allowed us to define two new intronic polymorphisms in phase, in the 5' and 3' boundaries of the exon 11 (GenBank accession number #DQ 869189).Altogether, our results suggest that the Crohn’s disease-linked CARD15 polymorphisms do not seem to predispose to idiopathic uveitis in the Spanish population.

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