scholarly journals Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangying Zhong ◽  
Ye Wang ◽  
Wenbin Lin ◽  
Zhenrong Yao ◽  
Jiang Zhang ◽  
...  

Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling.Case Report: A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (–α3.7/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (–α3.7/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses.Conclusion: This study enlarges the mutation spectrum of β-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen

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.


2020 ◽  
Author(s):  
Xi Luo ◽  
Shi-ping Chen ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Zhi-yu Peng ◽  
...  

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.


2016 ◽  
Vol 46 (2) ◽  
pp. 82 ◽  
Author(s):  
Pustika Amalia Wahidiyat ◽  
Djajadiman Gatot ◽  
Tenny Tjitrasari ◽  
Harapan Parlindungan Ringoringo ◽  
N S Marzuki ◽  
...  

Background Thalassemia is a monogenic disease, yet the clini-cal manifestations (phenotype) are variable although they havethe same genotype. The clear-cut correlation between genotypeand phenotype in β-thalassaemia/HbE patients remains unex-plained. There are several factors that play a role in the severity ofthe clinical manifestations, i.e. two alpha-gene deletion, homozy-gote Xmn1 polymorphism +/+, -+-++, ++-++ haplotype, and hemo-globin Constant Spring.Objective To understand the clinical diversity of patients with HbE/α thalassemia and to determine whether it is possible to predictphenotypic severity from genetic factors.Methods A descriptive study on clinical presentations and hema-tological data of beta-HbE thalassemia patients. DNA analysis wasperformed to detect β-thalassemia mutations and the amelioratingfactors (alpha-globin genes deletions and Xmn1 restriction site poly-morphism at position –158 upstream of the G γ-globin gene) whichwere already known.Results Thirty patients with HbE/β thalassemia (4 to 29 years old)were recruited. IVS1-nt5 (G>C) severe β + mutation was detectedin 20 patients. Eighteen of 20 patients with positive IVS1-nt5 mu-tation group were heterozygous for Xmn1 restriction site polymor-phism and none of the patients was co-inherited with two á-globingene deletion. Almost all patients (19/20) with positive IVS1-nt5mutation group required regular transfusions, yet the mean age atfirst blood transfusion was older in negative IVS1-nt5 mutation groupthan that of positive IVS1-nt5 mutation group (5.7 vs 4 years). Meanhemoglobin before initial transfusion was higher in negative IVS1-nt5 mutation group than that of positive IVS1-nt5 mutation group(5.88 vs 5.39 g/dl). The mean total transfusion per year was lowerin the negative IVS1-nt5 mutation group than that of positive IVS1-nt5 mutation group (190.6 vs 215.1 ml/year).Conclusions Beta-HbE thalassemia patients with identical betathalassemia mutation (IVS1-nt5) show remarkable clinical diver-sity. Neither two alpha-gene deletion, nor the Xmn1- G γ polymor-phism can explain the phenotypic variation. Other amelioratingdeterminants or genetic modifications responsible for the variableclinical severity remain to be explored.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5113-5113
Author(s):  
Jayasri Basak ◽  
Deboshree Majumdar ◽  
Nabamita Pal ◽  
Sanghita Paul ◽  
Soma Mukhopadhyay ◽  
...  

Abstract Abstract 5113 Background Toto is a primitive Indo-Bhutanese tribe residing in a small enclave called Totopara in the Jalpaiguri district of West Bengal, India. Toto culture and language is totally unique to the tribe, and is clearly distinguished from the neighboring Rajbongshis, Koch or the Bhutanese Sharchop tribes. Totos use to do consanguineous marriage and stay in the same locality even after marriage. Totos are becoming extinct since 1950. Total population of Totos are 1377 (smallest tribe of the world) and it is declining day by day. We noticed that their life span is very short (35-40 years). With a motive to investigate the reason behind it we started our work and got the answers of our queries. Almost 50% of them are carrier of beta Thalassemia, which is a genetic disease and are caused by the mutation of beta globin gene. The objectives of our study are, Materials & Methods After awareness program, 3-4 ml of blood sample was collected from each Toto along with their written consent. On the spot inexpensive NESTROF (Naked Eye Single Tube Red Cell Osmotic Fragility) test was done. After returning to institute we use to do CBC (Complete Blood Count) followed by HPLC (High Performance Liquid Chromatography). DNA was isolated from those samples detected as carrier or patients using the protocol standardized in our lab. Mutation was detected by ARMS (Amplification Refractory Mutation System)–PCR. Conclusion Total individual already screened in the Totopara under the age limit 10- 35 years is 688. Number of Totos and Non-Totos are 628 and 60 respectively. From NESTROFT and CBC result it was revealed that different blood parameters e.g., MCV, MCH, RBC, RDW, Hb% etc of 71% Totos do not match with the normal value and found to be significantly altered. HPLC results show that 51% Totos are carrier of HbE and 20% of them are HbE homozygous. Whereas 97% non-Totos are found to be normal. DNA analysis by ARMS-PCR confirmed the result of HPLC. The percentage of HbE carrier and HbE homozygous is very high among Totos and this is the real cause of their early death. To protect this primitive tribe we have to restrict their marriage between two carriers. For Totos thalassemia carrier detection should be mandatory before marriage. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Author(s):  
Zhiyang Guan ◽  
Zeyan Zhong ◽  
Hailin He ◽  
Dan Chen ◽  
Guoxing Zhong ◽  
...  

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 .


2006 ◽  
Vol 55 (5) ◽  
pp. 477
Author(s):  
In Jae Lee ◽  
Kwang Seok Eom ◽  
Seon Young Jeon ◽  
Im Kyung Hwang ◽  
Yul Lee ◽  
...  

2020 ◽  
pp. 51-56
Author(s):  
V.М. Аntonyuk-Kysil ◽  
◽  
І.Y. Dziubanovskyi ◽  
V.М. Yenikeeva ◽  
S.І. Lichner ◽  
...  

The objective: to evaluate the results of planned open surgical interventions (POSI) in pregnant women with primary symptomatic chronic vein disease (PSCVD). Materials and methods. The study included 457 pregnant women operated on a routine basis with PSCVD. The patients underwent ultrasound duplex angioscanning (USDA) of the veins of the lower extremities, inguinal canals, and iliac veins. The severity of the clinical manifestations of PSCVD was evaluated on a VCSS scale. With the help of the circadian visual-analog scale, the dynamics after the operative pain were studied. The effect of POSI on uterine tone and cardiac function of the fetus was investigated using cardiotocography. When forming the results for POSI, data from USDA, the severity of clinical and cosmetic manifestations of PCVD, the need for active prevention of thrombophlebetic, thromboembolic and hemorrhagic complications, minimization of surgical childbirth were taken into account. The results of treatment were studied in 2 groups of patients. Patients of the first group were treated with conservative therapy, the second group – POSI. Parametric indicators, which were presented as mean and standard error M(SD), were used for statistical data processing of the study, and their reliability was estimated using Student’s t-test. The species was determined to be significant at p<0.05. Results. 495 POSI were performed at 28-38 weeks gestation in an obstetric hospital (perinatal center), by a vascular surgeon from the staff of the center, who was familiarized with the peculiarities of working with this contingent of patients. Surgery was performed under local anesthesia in 346 (75.49%) pregnant women at one extremity, in 111 (24.51%) – at two in one session. According to the results of the study, it was noted that in the first group 33.7% of patients had a positive clinical result due to the reduction of pain syndrome, while 67.5% of patients had an increase and spread of varicose transformation in the area of saphenous and/or non-saphenous veins with spread of pathological venous reflux in the distal direction. 78% of patients had the need to administer prophylactic doses of low molecular weight heparins, both during pregnancy and in postpartum period. Out of 126 pregnant women with pronounced varicose veins of the external genital organs and perineum in 36 (28.6%) deliveries were performed by caesarean section. In 9 (3%) patients there was an acute thrombophlebitis of the subcutaneous veins of the lower extremities, which required 5 pregnant women to undergo urgent surgery when the inflammatory process had spread to the middle and above along the femoral vein of the large subcutaneous vein. Pregnant women of the second group with PSCVD on the basis of obstetric hospital (perinatal center) POSI were performed in the organization, which laid the ideology of the FTS program, strictly individual indications for intervention in the optimal terms of pregnancy, multidisciplinary management of patients, due to this in 93% of operated patients regression of clinical manifestations of the disease was noted, whch contributed to the correct and safe delivery of pregnancy with 100% absence of preterm birth, abnormalities in fetal development, pregnancy course, negative impact on obstetric and somatic condition of the pregnant woman. No hemorrhagic, thrombophlebic, thromboembolic complications were noted. Patients in the postoperative period did not require medical support, as during the period of pregnancy, during delivery and in the postpartum period. There were no indications for surgical delivery. 2.4% of patients experienced complications of post-operative wounds in the form of cheese, which had no effect on pregnancy and was eliminated before delivery. In the postoperative period, if necessary, it was recommended to use elastic compression class garments 1–2. Conclusion. POSI made at PSCVD in optimal terms of pregnancy in a specialized obstetric hospital by a vascular surgeon in strictly individual indications is safe, both for the fetus and the pregnant woman. It is promising to further study the results of POSI in pregnant women with PSCVD to introduce it into the arsenal of treatment of this pathology. Key words: FTS ideology, planned open surgical interventions in pregnant women.


1970 ◽  
Vol 5 (4) ◽  
pp. 51-60
Author(s):  
José Henrique Pereira Pinto ◽  
Renan Lemos de Toledo ◽  
William do Prado Franquelo

RESUMOIntrodução: Alergia à Proteína do Leite de Vaca (APLV) é uma doença inflamatória secundária à reação imunológica contra uma ou mais proteínas do leite de vaca (LV) que afeta principalmente a faixa pediátrica. A real prevalência é discutida em muitos estudos. As manifestações clínicas dependem do tipo da resposta imunológica, ser IgE mediada ou não. Os sintomas se iniciam por volta dos 06 meses de vida e na maioria dos casos, esse processo alérgico regride, com o paciente desenvolvendo tolerância até a adolescência. Casuística: Relata-se um caso de um paciente do sexo masculino, apresentando desde os 6 meses de idade de anafilaxia e broncoespasmo. Nesta época foi levado em hospitais e ambulatórios sendo diagnosticado e tratado como asma apenas, porém sem sucesso. Aos 18 anos, em consulta com especialista foi diagnosticado com APLV, apesar da dieta de exclusão, apresentou diversas reações anafiláticas, devido a ingestão acidental do alérgeno. Discussão: O paciente iniciou os primeiros sintomas quando houve contato com LV e apresentou teste laboratorial com valores compatíveis a patologia. Segundo a literatura a prevalência de APLV cai para menos de 1% aos 6 anos de vida e está persistência pode estar associada a múltiplos fatores, no caso relatado, o paciente não apresentou tolerância até o presente momento. Conclusão: APLV é uma doença usualmente de criança em que, se estas não adquirirem tolerância, complicações podem perdurar indefinidamente. O Diagnóstico precoce e o manejo adequado desta condição, revela grande importância na qualidade de vida e na prevenção de anafilaxia.Palavras chave: Alergia, Proteína do leite de vaca, Anafilaxia. ABSTRACT Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease Introduction: Allergy to cow's milk (CMPA) is an inflammatory disease secondary to immune response against one or more cow's milk proteins (LV) which primarily affects pediatric patients. The current prevalence is discussed in many studies. The clinical manifestations depend on the type of immune response, being IgE mediated or not. Symptoms start at about 06 months of life and in most cases, the allergic process subsides, and the patient develops tolerance through adolescence. Case Report: We report the case of a male patient, who was presenting, since his 06 months of age, anaphylaxis and bronchospasm. At that time he was taken into hospitals and clinics being diagnosed and treated as asthma, but without success. At 18, in consultation with expert was diagnosed with CMPA, and despite the exclusion diet, presented several anaphylactic reactions due to accidental ingestion of the allergen. Discussion: The patient began the first symptoms when there was contact with LV and presented laboratory test values compatible with the pathology. According to the literature the prevalence of CMPA drops to less than 1% to 6 years of life and this persistence can be associated with multiple factors, in our case, the patient did not develop tolerance to date. Conclusion: CMPA is usually a child disease but ,if they do not acquire tolerance, complications can last indefinitely. Early diagnosis and appropriate management of this condition, reveals a great deal on quality of life and prevention of anaphylaxis. Keywords: Allergy, Cow’s milk protein, Anaphylaxis. 


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