粤北地区地中海贫血检出率及基因分型的调查分析

目的 了解粤北地区地中海贫血的发病情况及基因分型。方法 红细胞休克-管定量法对所有受检人进行地贫筛查，对地贫筛查阳性的标本进一步采用PCR法进行α地贫1基因检测，用PCR结合反向点杂交法(RDB)，进行β地贫的基因检测。结果 在1010例受检者中，地贫筛查阳性的有118例，占受检总人数的11．6％。地贫筛查阳性的所有标本均进行了α地贫1基因检测，诊断为α地贫1杂合子的有69例，占受检总数的6．83％，32例进行了β地贫基因检测，其中21例为β地贫杂合子，占受检总数的2．1％，其基因突变类型分别是：CD41—42(-TTCT)突变12例，IVS-2—654(C→T)突变2例，-28(A→G)突变2例，CD17(A→T)突变2例，71-72( A)突变2例，27—28( C)突变1例。结论 粤北地区地中海贫血发生率较高。做好婚前及产前地贫筛查及产前基因诊断等工作，对避免重型地贫患儿的出生，具有重要意义。     

儿童地中海贫血的发生率及发病基因分析

目的调查广州地区儿童地中海贫血（地贫）的发生率及其中国人常见发病基因的分布特征。方法对4990例广州地区儿童进行以全自动凝胶电泳为主的地贫血液学检查,并利用以缺口PCR（gap-PCR）为原理的单管多重PCR方法、PCR结合反向斑点杂交（PCR-RDB）法分别对筛查出的287例患儿（其中α地贫103例、β地贫177例、α合并β7例）进行中国人常见发病基因的诊断分析。结果（1）在4990人中,检出α地贫427人,发生率为8.56%;检出β地贫562人,发生率为11.26%;α合并β7人,发生率为0.14%。（2）进行基因分析的110例α地贫（包括α合并β的7例）全部都是缺失型,其中东南亚缺失型（--SEA）占72.80%,右侧缺失型（-α^3.7）占18.38%,左侧缺失型（-α^4.2）占8.82%。进行基因分析的184例β地贫有181例得到确诊,共检出10种突变基因,22种基因型,最多见的前5种依次是：CD41-42（45.71%）,IVS-Ⅱ-654（25.79%）,CD17（14.03%）,TATbox-28（8.15%）,CD71-72（3.17%）。结论广州地区是国内α和β地贫发生率较高和β地贫基因背景最复杂的地区,在地贫高发区应加强对儿童人群进行地贫的血液学筛查和常见基因的诊断。     

The prevention of thalassemia in Sardinia

In this paper we review the characteristics and effectiveness of a program aimed at preventing homozygous beta-thalassemia in the Sardinian population. The target population for screening were couples at marriage, conception or early pregnancy. Awareness of the problem and the involvement of the population were achieved via the mass media or by personal approaches through lectures or discussions. Parents' Associations were consulted and have made themselves available to prospective couples in several critical areas. Education on thalassemias was introduced into the school curriculum. Counseling was based on private interviews at which the several options available were discussed with the individual carrier or the couples. Prenatal diagnosis was chosen by the large majority of couples counseled. The introduction of 1st trimester diagnosis resulted in a striking increase of the acceptance rate from 93.2 to 99.1%. Prenatal diagnosis was carried out initially by fetal blood analysis and thereafter by trophoblast or amniocyte DNA analysis. Direct detection of the mutation by oligonucleotide hybridization on agarose gel separated DNA fragments or by dot-blot analysis with allelic specific oligonucleotide probes on enzymatically amplified DNA was used. This program resulted in a decline in thalassemia major births of 90%. The reasons for residual cases were mostly lack of information and, less frequently, misdiagnoses or refusal of fetal diagnosis.     

Parent-Child Interactions in Clinically Anxious Children and Their Siblings

Examines the value and importance of theory in child psychology, particularly with respect to clinical practice. Although it is readily apparent that theory is not an essential element of treatment, the role of theory is to provide a coherent framework for clinical intervention. Theory provides a foundation for understanding the presenting pathology, the factors that affect it, the patient's and therapist's roles within the context of treatment, and the specific intervention strategies to be utilized. Therapeutic commonalities are considered as they may affect treatment outcome, but they are not viewed as the essential factors in efficacy. The value and meaning of eclecticism are also discussed.     

Siblings with carbamyl phosphate synthetase i deficiency

This paper concerns with two autopsied cases of siblings who died from cerebral disturbances. In these patients hyperammonemia developed in the neonatal phase due to carbamyl phosphate synthetase I (CPS I) deficiency. The patient in Case 1 was admitted 2 days after birth because of oliguria and vomiting. Hyperammonemia developed and she died on the 43rd day. In Case 2 hyperammonemia developed from the 2nd day after birth and she expired on the 42nd day. In both cases the diagnosis of CPS I deficiency was established from autopsy findings of the liver. Acta pathol. jpn. 34: 901～910, 1984.     

Bone marrow transplantation in patients with thalassemia

We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.     

湖北地区84例地中海贫血基因诊断分析

目的预防地中海贫血患儿的出生,减少出生缺陷。方法基因诊断采用多聚酶链反应（polymerase chain re-action,PCR）和反向斑点杂交（reverse dot blot,RDB）技术。结果湖北地区84例疑诊患者共检出44例阳性,其中β-地中海贫血为37例。结论湖北地区也应加强地中海贫血的筛查,以减少地中海贫血患儿的出生。     

孪生新生儿的地中海贫血实验分析

目的 探讨广东省的孪生新生儿中地中海贫血（THAL）状况，提高诊断孪生新生儿地中海贫血的实验水平。方法 日本东亚公司SYSMEXNE1500全自动血细胞分析仪检测血常规，美国HELENA公司全自动快速电泳系统（REP）及其pH8．6琼脂凝胶试剂作血红蛋白区带定量。结果 共检测219例孪生新生儿，正常组82例，地中海贫血组137例，分为4组：轻型α-THAL静止型组69例，轻型α-THAL标准型组29例，轻型β-THAL组30例，轻型α-THAL组复合轻型β-THAL组6例，另外还有α-THAL中间型（HbH型）1例，异常HBE杂合子2例。在血常规中RBC、MCV、MCH和RDW-CV四项检测中，轻型α-THAL标准型组和轻型β-THAL组与正常组比较有非常显著差异（P〈0．01）；尤其轻型α-THAL标准型组显示最明显的小细胞低色素性贫血，MCV〈95fL，MCH〈35；在血红蛋白电泳的HbA定量分析中，特别是轻型β-THAL组与正常组比较有非常显著差异（P〈0．01），轻型β-THAL组的HBA值〈16％，正常组HbA值25．0％。孪生新生儿可出现各种不同的THAL状况，在双孪双胎的孪生新生儿中有出现轻型α-THAL组复合轻型β-THAL的、正常新生儿与异常血红蛋白E杂合子的、轻型α-THAL静止型与α-THAL中间型（HbH）等多种状况。结论 孪生新生儿（足月儿）脐血检测血常规和血红蛋白电泳区带定量是诊断新生儿地中海贫血的重要指标，应认真建立新生儿血常规的正常参考值。     

Acquired sea-blue histiocytosis in beta thalassemia major

Primary sea-blue histiocytosis is a rare syndrome. Secondary or acquired sea-blue histiocytosis occurs in a wide array of hematologic and systemic disorders, rarely these cells have been found in cases of thalassemia. A case of sea-blue histiocytosis in a patient of thalassemia is being reported for its rarity.     

Fatal Lymphoproliferative Disease in Two Siblings Lacking Functional FAAP24

Hereditary defects in several genes have been shown to disturb the normal immune response to EBV and to give rise to severe EBV-induced lymphoproliferation in the recent years. Nevertheless, in many patients, the molecular basis of fatal EBV infection still remains unclear. The Fanconi anemia-associated protein 24 (FAAP24) plays a dual role in DNA repair. By association with FANCM as component of the FA core complex, it recruits the FA core complex to damaged DNA. Additionally, FAAP24 has been shown to evoke ATR-mediated checkpoint responses independently of the FA core complex. By whole exome sequencing, we identified a homozygous missense mutation in the FAAP24 gene (cC635T, pT212M) in two siblings of a consanguineous Turkish family who died from an EBV-associated lymphoproliferative disease after infection with a variant EBV strain, expressing a previously unknown EBNA2 allele.In order to analyze the functionality of the variant FAAP24 allele, we used herpes virus saimiri-transformed patient T cells to test endogenous cellular FAAP24 functions that are known to be important in DNA damage control. We saw an impaired FANCD2 monoubiquitination as well as delayed checkpoint responses, especially affecting CHK1 phosphorylation in patient samples in comparison to healthy controls. The phenotype of this FAAP24 mutation might have been further accelerated by an EBV strain that harbors an EBNA2 allele with enhanced activities compared to the prototype laboratory strain B95.8. This is the first report of an FAAP24 loss of function mutation found in human patients with EBV-associated lymphoproliferation.     

广东广西交界地区地中海贫血发生率及基因检测结果分析

目的研究两广交界地区地中海贫血的检出率及其基因分布，预防地中海贫血重症患儿的出生，减少出生缺陷。方法采用红细胞平均体积（MCV）、红细胞脆性试验及血红蛋白电泳三项联合测定对2503例进行地中海贫血筛查；用单管多重PCR（gap—PCR）及DNA芯片反向点杂交（RDB／PCR）检测技术，分别对初筛阳性者进行α、β地中海贫血基因检测。结果2503例受检者中筛查阳性502例，初筛阳性率为20．06％。502例接受地贫基因诊断，411例确诊为地中海贫血，检出率为81．87％。总检出地贫基因携带率（包括仅和B地贫）为16．42％，其中α地贫基因检出率为9．44％，基因型-SEA/αα、--SEA／αα^cs、SEA／α^3.7这三种类型的比例最高，共占72．38％；B地贫基因检出率为8．15％，共检出8种B地贫基因类型，其中CD41—42（-TTCT）、TATAbox一28（A→G）、CD17（A→T）、IVS-Ⅱ654（c→T）及CD71—72（＋A）5种突变类型占98．04％。检出α和β地贫双重杂舍子32例。结论两广是地中海贫血的高发区，应加强对人群进行地贫的血液学筛查和基因诊断，本研究同时进行仅地贫的缺失型与非缺失型及β地贫的基因诊断，有效地提高地贫的检出率，对优生优育、干预重症地贫儿出生有着重要作用。     

Molecular genetics of alpha thalassemia

Linked duplicate genes in Chromosome 16 condition the production not only of alpha-globin chains in the Hemoglobin A (HbA) molecule, but also of the varied forms of alpha thalassemia in human subjects. Null allelism, not gene deletion, exists at these gene loci. Two codominant alleles occur at each locus; these are characterized as Gb and Ob at one locus, and as Gc and Oc at the second locus. Gb and Gc are genetically active alleles, and either conditions the production of alpha-globin chain. Ob and Oc are null or genetically inert alleles, and neither conditions the production of alpha-globin chain. Gb and Gc are additive in the expression of disease genotype. The number of alpha-globin chains in the HbA molecule, and the absence as well as the varied forms of alpha thalassemia are inherited quantitatively as follows: four alpha-globin chains and the absence of alpha thalassemia result from GbGbGcGc; either GbGbGcOc or GbObGcGc yields three alpha-globin chains and asymptomatic alpha thalassemia minor; any one of three genotypes, GbGbOcOc, GbObGcOc or ObObGcGc, yields two alpha-globin chains and mild alpha thalassemia minor; either GbObOcOc or ObObGcOc yields one alpha-globin chain and severe alpha thalassemia minor; ObObOcOc produces no alpha-globin chain and the fetal alpha thalassemia major. The inheritance of any combination of active and null alleles, and of the associated forms of alpha thalassemia, is deducible from the alpha-globin as well as the disease phenotypes and/or genotypes of parental subjects.