An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene

The gene for autosomal recessive spinal muscular atrophy (SMA) has been mapped to 5q12 in a region that contains repeated markers and genes. Three cDNAs that detect deletions in SMA patients have been reported. One of these, the survival motor neuron (SMN) cDNA, is encoded by two genes (SMNT and SMNC) which are distinguished by base changes in exons 7 and 8. Exon 7 of the SMNT gene is not detectable in approximately 95% of SMA cases, due either to deletion or sequence conversion. There is limited information on the mutations in SMA patients that have detectable SMNT, these are critical for confirmation of SMNT as the SMA gene. Using SSCP analysis of the SMN exons we screened our SMA patients that possess at least one intact SMNT allele for mutations in SMNT. We identified one type I SMA patient with an 11 bp duplication in exon 6 which causes a frameshift and premature termination of the deduced SMNT protein. Dosage and SSCP analysis of SMNT in this family indicated that the father contributed a SMNT-deleted allele to the affected child whereas the mother passed on the 11 bp exon 6 duplication SMNT allele. Analysis of RNA by RT-PCR conclusively demonstrated that the 11 bp duplication is associated with the SMNT locus and not SMNC. This mutation provides strong support for SMN as the SMA-determining gene and indicates that disruption of SMNT on its own is sufficient to produce a severe type I SMA phenotype.      

支气管动脉栓塞术后并发症的预防及护理

0　引言　大咯血原因很多 .炎症、支气管扩张、肺癌、肺结核、肺动静脉瘘等 .但因支气管动脉畸形引起的大咯血尚未见专题报道 .现将我院 1992年 10月份以来行数字减影血管造影 (DSA )检查 ,确诊支气管动脉畸形行支气管动脉栓塞(BAE)治疗大咯血术后并发症的预防与护理报道如下 :1　临床资料　 6 (男 5 ,女 1)例大咯血患者 ,年龄 16～ 5 9岁 .均因无明显诱因 ,反复咯血而多次保守治疗 ,一次或 2 4h内咯血量为 40 0～ 10 0 0 m L ,病程最长 13a.入院后行 CT、纤维支气管镜、支气管碘油造影等栓查 ,均未见明显异常 ,后因保守治疗无效时行 D…     

低频电交变磁场治疗静脉炎136例疗效分析

0引富静脉炎是静脉血管常见的一种炎性病变．常由感染、组织损伤、静脉滴注化学药物刺激引起．常侵犯浅静脉,临床治疗多采用药物治疗和局部湿热敷方法「’-,疗效较差本组136例由于手术和静脉化学药物等引起静脉炎患者,我们采用磁疗机局部治疗,不用抗菌素及外用药,收?..     

Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia

Raine syndrome is an osteosclerotic bone dysplasia, which has proved to be lethal within the first few weeks of life in all the reported cases to date. We recently identified a chromosomal rearrangement and telomeric microdeletion in a patient with Raine syndrome and subsequently identified mutations in the FAM20C gene, located within the deleted region, in six additional Raine syndrome cases. The phenotype of Raine syndrome in the cases examined was remarkably consistent with generalized osteosclerosis of all bones, periosteal bone formation, characteristic facial phenotype and lethal within the first few weeks of life. In the current study, we have identified two unrelated individuals who presented at birth with a sclerosing bone dysplasia with features very similar to those in Raine syndrome but who survived infancy and are now aged 8 and 11 years, respectively. Mutations in FAM20C, consistent with autosomal recessive inheritance, were identified in both cases. In the first case, a homozygous non-synonymous mutation in exon 7 (1309G>A D437N) was identified, and in the second case, compound heterozygosity for non-synonymous mutations in exon 2 (731T>A I244N) and in exon 3 (796G>A G266R) was revealed. Raine syndrome has been previously considered to be a neonatal lethal condition. However, the identification of mutations in these two patients confirms a broader phenotypic spectrum and that mutation of FAM20C does not always lead to the infantile lethality previously seen as a prerequisite for Raine syndrome diagnosis.     

Application of a computer program to exclude additional unexpected antibodies

BACKGROUND : When a patient has produced red cell (RBC) antibodies in the past, he or she is at risk of producing additional antibodies after antigen challenge. The presence of these antibodies should be excluded before each transfusion. The following criteria are applied when using commercial test RBCs: RBCs should not express the antigen against which the previously documented antibody is directed. For other clinically significant antigens, at least one RBC sample should be from a donor who is homozygous for the encoding gene. The manual selection of such RBCs is tedious and requires experience. STUDY DESIGN AND METHODS : A computer program has been developed that generates exclusion panels (EPs) by selecting a minimum number of RBCs from commercial test panels complying with current criteria. When RBCs from a donor who is homozygous for the encoding gene are absent, the program selects, as a second-best option, RBCs from a donor who is heterozygous for that gene. The computer program developed for this study investigated the usefulness of commercially available panels from separate manufacturers in excluding the presence of additional antibodies. A list of 488 antibodies detected by a regional blood bank in 1994 was used as cases of antibodies documented in the past. RESULTS : In 61 percent of the cases, successful EPs (i.e., those complying with the criteria), consisting of three to four different phenotypes, were selected. In the remaining 39 percent of cases, it was impossible to generate successful EPs: 1 to 2 additional antibodies could not be excluded or could be excluded only by using RBCs from heterozygotes. Commercial panels differed only slightly in their efficiency in providing suitable RBCs. None of the commercial panels could provide suitable RBCs to exclude all additional antibodies in the presence of anti-c, anti-e, or anti-M. Increasing the number of RBCs from which to select EPs only slightly increased the percentage of success. CONCLUSION : Computer-aided construction of EPs quickly shows whether strict criteria can be met or whether alternative techniques should be used. It leads to a significant reduction in the number of RBC suspensions necessary to exclude additional antibodies. Results with various commercial panels differed only slightly.     

ERRATA

Summary (p. 747): The frequency of upper GI bleeding in maleRA patients is 13.2% and not 1.2%. Table III (p. 749): The frequencyof gastriculcer in male patients of the index group is 8.2%and not 89.2%. This is not significantly different from thefrequency of gastric ulcer in male patients of the referencegroup being 2.4%. However, the frequency of gastric ulcer infemale patients of the index group (5.8%) is significantly differentfrom the frequency of gastric ulcer in female patients of thereference group (0.5%; P<0.005).     

Crotalocytin: recognition and purification of a timber rattlesnake platelet aggregating protein

After being envenomated by the timber rattlesnake, a patient was found to have a platelet count of 5000 per microliter, prothrombin time and activated partial thromboplastin time both greater than 150 sec, plasma fibrinogen 0 mg/dl, and fibrinogen split products 2560 microgram/ml. However, this patient did not appear to have acute disseminated intravascular coagulation since coagulation factors II-XII were normal. We postulated that this venom contained, in addition to a fibrinogen clotting enzyme, a platelet activating protein, Crotalocytin. Crotalocytin was purified from crude timber rattlesnake venom by Sephadex G-100 gel-filtration, low ionic strength precipitation, and DEAE-A50 Sephadex chromatography. By sodium dodecyl sulfate gel electrophoresis and gel-filtration Crotalocytin was a single chain polypeptide, molecular weight 55,000. Thrombocytopenia after timber rattlesnake bite appeared to be due to a protein that directly activated platelets. Timber rattlesnake bite mimicked the clinical presentation of disseminated intravascular coagulation.     

Human fetal bone marrow early progenitors for T, B, and myeloid cells are found exclusively in the population expressing high levels of CD34

Experimentation on human stem cells is hampered by the relative paucity of this population and by the lack of assays identifying multilineage differentiation, particularly along the lymphoid lineages. In our current study, phenotypic analysis of low-density fetal bone marrow cells showed two distinct populations of CD34+ cells: those expressing a high density of CD34 antigen on their surface (CD34hi) and those expressing an intermediate level of CD34 antigen (CD34lo). Multiple tissues were used to characterize the in vitro and in vivo potential of these subsets and showed that only CD34hi cells support long-term B lymphopoiesis and myelopoiesis in vitro and mediate T, B, and myeloid repopulation of human tissues implanted into SCID mice. CD34lo cells repeatedly failed to provide long-term hematopoietic activity in vivo or in vitro. These results indicate that a simple fractionation based on well-defined CD34 antigen levels can be used to reproducibly isolate cells highly enriched for in vivo long-term repopulating activity and for multipotent progenitors, including T- and B-cell precursors. Additionally, given the limited variability in the results and the high correlation between in vitro and in vivo hematopoietic potential, we propose that the CD34hi population contains virtually all of the stem cell activity in fetal bone marrow and therefore is the population of choice for future studies in hematopoietic stem cell development and gene therapy.