广西柳州地区αβ复合型地中海贫血基因突变类型及检出率分析

目的研究广西柳州地区αβ复合型地中海贫血（地贫）基因突变类型及检出率。方法采用膜反向杂交技术检测β地贫基因。用gap-PCR法检测三种常见α地贫缺失基因型：东南亚型缺失（--SEA）、右侧缺失（-α^3.7）、左侧缺失（-α^4.2）。结果153例β地贫中检测出30名α地贫,检出率为19.61%。均为轻型β地贫复合α地贫,其中β地贫杂合子复合--SEA/αα占90.00%,β地贫杂合子复合-α^3.7/αα占3.33%,β地贫杂合子复合-α^4.2/αα占6.67%。结论广西柳州地区αβ复合型地贫检出率高。--SEA/αα是本地区β地贫杂合子检出的主要复合α地贫基因型。准确诊断β地贫合并α地贫双重杂合子对正确进行遗传咨询,搞好优生优育十分重要。     

Molecular characterization and origins of Hb Constant Spring and Hb Paksé in Southeast Asian populations

Hemoglobin Constant Spring (Hb CS) and Hb Paksé, two abnormal Hbs characterized by elongated α-globin chains resulting from mutations of the termination codon in the α2-globin gene, are the most prevalent nondeletional α-thalassemias in Southeast Asia. To determine the origins of these two variants in the region, we have determined α-globin gene haplotypes associated with these two variants on 120 Thai, eight Cambodian, and six Laos alleles, and the results were compared with those reported previously for the Chinese and Mediterranean. Five haplotypes were found to be associated with 131 α^CS genes examined, whereas a single haplotype was linked to all the α^Paksé genes in these Southeast Asian populations. All the α^CS haplotypes differed from those of the Mediterranean, but one of them was similar to a Chinese α^CS gene reported previously. It is concluded that there are multiple origins of the α^CS and a single origin of the α^Paksé mutations in Southeast Asia. Hematological findings confirm the mild thalassemia intermedia phenotypes for pure homozygous Hb CS and homozygous Hb CS with Hb E heterozygote and Hb E homozygote. The appearance of Hb CS peak by high-performance liquid chromatography analysis indicates the ability to form a tetrameric Hb molecule between the α^CS and β^E chains, leading to a novel derivative with similar characteristics to Hb CS.     

G6PD缺乏对地中海贫血产前筛查血液学指标的影响

目的探讨葡萄糖6磷酸脱氢酶（G6PD）缺乏对地中海贫血基因携带者平均红细胞容积（MCV）、红细胞平均血红蛋白含量（MCH）的影响。方法2006-06—2008—12产前筛查的孕妇及其丈夫中行地中海贫血基因分析确诊为地中海贫血基因携带者,常规行C6PD酶活性测定及血细胞分析。分为C6PD缺乏组及G6PD正常组,比较两组的MCV、MCH。结果α地贫-1合并G6PD缺乏组MCV、MCH显著高于α地贫-1不合并C6PD缺乏组（P〈0．05）,轻型β地贫合并G6PD缺乏组MCV显著高于轻型β地贫不合并G6PD缺乏组（P〈0．05）,轻型β地贫合并G6PD缺乏组MCH高于轻型β地贫不合并G6PD缺乏组,但差异无统计学意义。结论G6PD缺乏可影响MCV、MCH筛查地贫的敏感性而造成漏诊,因此建议常规应用血细胞分析、血红蛋白电泳、红细胞渗透脆性联合筛查地中海贫血,并同时检测G6PD活性,以提高地贫基因携带者的检出率,减少出生缺陷。     

桂林市城镇育龄人群地中海贫血现况调查

目的 调查桂林市城镇育龄人群地中海贫血(地贫)的现况.方法 用红细胞平均容积(MCV)和血红蛋白电泳法对所有调查对象进行地贫筛查,对筛查出疑为α地贫或β地贫标本进一步采用PCR结合反向点杂交法(ROB)进行基因检测,以检出地贫基因来确诊.结果 在1580例受检者中,确定α地贫基因型的有79例,检出率为5.00%,α贫在男女性中检出率分别为5.32%、4.68%,差异无统计学意义(X2=3.04,X2＜X0.05(1)=3.84,P＞0.05);确定β地贫基因型的有114例,检出率为7.22%,β地贫在男女性中检出率分别为7.85%、6.58%,差异无统计学意义(X2=0.95,X2＜X0.05(1)=3.84,P＞0.05);总的地贫检出率为12.22%(193/1580).α地贫共检出10种基因型,以轻型--SEA/αα为主,检出率为3.54%;静止型以-α3.7/αα居多,轻型以--SEA/αα居多,中间型以--SEA/-αCS居多;其构成比分别为7.59%、70.88%、2.53%;B地贫共检出7种基因型,以CD41-42(-TTCT)居多,检出率为3.16%,其中最常见的3种基因型CD41-42(-TTCT)、CDl7(A→T)和IVS-Ⅱ-654(C→T),构成占突变基因的87.71%;β、α复合型地贫检出率为0.63%.结论 桂林市城镇育龄人群地贫检出率较高.     

地中海贫血筛查及其联合试验的临床应用评价

目的：分析红细胞脆性及血红蛋白电泳单项检测及其联合试验在地中海贫血筛查中的临床意义。方法：对经分子生物学方法确诊的96例地中海贫血标本及92例非地中海贫血标本的结果进行统计学分析。结果：红细胞脆性及血红蛋白电泳对诊断地中海贫血的灵敏度和特异度分别为85．39％、81．72％及79．80％、78．95％。红细胞脆性及血红蛋白电泳平行联合试验的灵敏度和特异度分别为97．33％和63．00％,串联联合试验的灵敏度和特异度分别为69．78％和95．75％。结论：在地贫的诊断试验申,红细胞脆性和血红蛋白电泳平行联合试验可提高灵敏度,串列联合试验可提高特异度,联合试验较单项检测具有一定的优越性。     

南宁地区新生儿地中海贫血筛查结果分析

摘要:目的　在南宁地区新生儿中进行地中海贫血（地贫）筛查,为临床诊断和早期治疗提供依据。方法　应用毛细管电泳法对19 419例新生儿干血斑进行血红蛋白分析,对筛查阳性新生儿召回进行地贫基因分析。结果　19 419例样本中,检出α地贫表型2 085例,β地贫表型1 428例,包括α合并β地贫77例,异常血红蛋白121例。1 085例进行基因分析,α地贫确诊符合率为94.16%（645/685）显著高于β地贫的41.10%（164/399）（χ2＝430.067,P＜0.01）,基因型以αα/--SEA、CD41-42（-TCTT）最常见。α地贫确诊率男与女（χ2＝0.029,P＞0.05）、壮族与汉族间（χ2＝0.028,P＞0.05）差异无统计学意义,β地贫确诊率女性高于男性（χ2＝17.207,P＜0.01）、壮族显著高于汉族（χ2＝9.539,P＜0.01）。结论　南宁地区新生儿地贫的基因突变类型、携带率及表型与人群有关,在本地区开展新生儿地贫筛查很有必要。     

产前筛查高风险的临床认识与干预策略

产前筛查是预防出生缺陷的第2道关键防线,必要的产前常规筛查是杜绝出生缺陷的手段.采用血清学对唐氏综合征妊娠早期筛查和妊娠中期联合筛查,神经管畸形筛查,分子生物技术对地中海贫血的筛查及确诊,产前超声对胎儿体表、内脏器官及骨骼畸形等先天性疾病筛查,从中发现高风险人群.并以生物遗传因素技术为主导,选择适时的产前诊断,提高对胎...     

Pulmonary function tests in beta thalassemia

To study pulmonary function tests (PFT) in multiple transfusion recipient thalassemics, PFTs were done for 30 thalassemics and 20 matched controls. Confirmed cases of thalassemia on regular transfusion therapy were the subject of study. Apart from history and physical examination of the thalassemics, serum ferritin estimation and spirometry were done. Parameters studied included lung volumes—functional residual capacity (FRC), forced vital capacity (FVC), residual volume (RV) and total lung capacity (TLC); and flow rates —forced expiratory volume in one second (FEV,), forced expiratory volume in 1 second/forced vital capacity (FEV,/FVC), peak expiratory flow 25–75 (PEF 25–75%) and peak expiratory flow rate (PEFR). Single breath carbon monoxide diffusing capacity (DLco) and arterial blood gas (ABG) were also analysed. The mean height and weight of thalassemics were below that of age matched controls. A restrictive abnormality in PFT was found in 86.6% cases. These patients were found to have a decrease in all the lung volumes namely FVC, FRC, RV and TLC with a proportional decrease in the flow rates, FEV1, PEF 25–75% and PEF with a normal (> 0.75) FEV1/FVC ratio. DLco was decreased in all the patients with restrictive lung disease and fall in DLco showed a good correlation (r = 0.7, P <. 001) with the severity of restrictive disease suggesting that some intrapulmonary pathology is likely to be responsible for the restrictive pattern. None of the cases had an obstructive or mixed pattern of pulmonary dysfunction. No correlation was found between severity of restrictive disease and the serum ferritin levels. A negative correlation with degree of hepatosplenomegaly was found. No correlation was found between severity of the defect and age, number of blood transfusions received and hemoglobin at the time of doing the test. To conclude, restrictive lung disease is the predominant abnormality in multi-transfused thalassemics, which is probably due to pulmonary parenchymal pathology. The abnormality of PFTs is not directly related to iron overload.     

地中海贫血表型阳性平均红细胞体积和平均血红蛋白浓度截断值及应用

目的 探讨平均红细胞体积(MCV)和平均血红蛋白浓度(MCH)在地贫筛查中的诊断截断值及应用价值.方法 在南宁农村育龄夫妇地贫筛查中以血清铁蛋白正常的经基因分析确认的153例健康成人、55例β地贫杂合子、76例α地贫1、59例α地贫2和18例不贫血或只有轻度贫血的αβ复合型地贫MCV和MCH通过受试者工作曲线确定其地贫筛查截断值,并以确定的截断值分析其临床诊断意义.结果 诊断地贫的截断值分别为MCV≤78.25fl和MCH≤25.65pg,此截断值的敏感度和特异度分别为MCV:85.6%和94.8%,MCH:82.7%和94.8%.55例β地贫杂合子和18例复合型地贫MCV和MCH均低于上截断值,76例α地贫1除1例MCH高于截断值外其它均低于截断值,59例α地贫2中30例MCV低于上截断值,24例MCH低于上截断值,而健康成人中分别有8例MCH和/或 MCV低于上截断值.结论 以MCV≤78.25fl和MCH≤25.65pg作为地贫表型阳性截断值进行地贫筛查有较高的应用价值.     

南宁地区14096例儿童地中海贫血筛查与基因诊断分析

目的了解南宁地区儿童地中海贫血（TM）发生情况、基因突变类型及频率。方法通过全血细胞分析、血清铁蛋白检测对南宁地区14096例儿童进行TM初步筛查,对筛查结果阳性者进行α—TM或（和）β—TM基因突变检测。结果初步筛查阳性2594例,阳性率18．40％,进一步经基因分析确诊TM1878例,检出率13．32％,其中α—TM和β-TM分别为1161例（8．24％）和855例（6．07％）,其中包括α—TM合并β—TM138例（0．98％）,中间型、重型TM334例（2．37％）。检出α-TM基因型共22种,以- -．＊^sea／αα为主,占49．79％;β—TM基因型共28种,以CD41-42（-TCTT）／N和CD17（A→T）／N为主,分别占40．70％和25．73％。6种α-等位基因1410个,以--^sea为主,突变率为2．84％;10种β-突变位点967个,以CD41-42（-TCTT）和CD17（A→T）为主,突变率为1．59％和0．98％。结论南宁地区儿童TM发生率高,TM基因突变类型多,应加强育龄人群及新生儿期TM筛查,以降低TM相关出生缺陷率,早期干预治疗。