马凡综合征微纤维蛋白1基因突变检测及单倍型连锁分析

目的：检测中国人马凡综合征（Marfan syndrome,MFS)患者微纤维蛋白1（fibillin-1,FBN1)基因的突变及对马凡综合征患者的家系成员进行症状前诊断。方法：应用聚合酶链反应－单链构象多态性技术和测序方法，对汉族9个家系中共17个MFS患者进行基因突变检测；运用FBN1基因内4个内含子中的可变串联重复序列构建染色体单倍型，进行家系单倍型连锁分析和基因诊断。结果：发现MFS（A）家系Ⅱ1患者有单链构象改变，测序证实为位于FBN1基因第25号外显子3243－3256核苷酸之间有I个13bp的小片段缺失，为新位点基因移码突变，其序列为gcctctgcaccca;单倍型连锁分析发现MFS（B）家系Ⅲ1是1个无症状期患者。结论：中国人FBN1基因突变可以引起马凡综合征，应用突变检测与单倍型连锁分析方法能为马凡综合征基因诊断提供依据。     

甘肃省SARS抗体血清流行病学调查

目的 了解甘肃省严重急性呼吸综合征(SARS)患者、密切接触者和正常人群血清SARS冠状病毒特异性IgG抗体水平。方法 利用酶联免疫吸附试验(ELISA)法检测SARS病毒IgG抗体水平。检测对象包括甘肃省9例SARS患者的急性期和(或)恢复期系列血清，l109例直接护理SARS患者的医生、护士、实验室检测人员、疾控人员和曾与患者有接触的人员以及978例正常人血清。结果 9例临床诊断病例SARS冠状病毒特异性IgG抗体中6例为阳性，疾病恢复后12个月血清抗体仍为阳性；密切接触者1例特异性IgG抗体阳性；正常人3例特异性IgG抗体阳性。结论 病例抗体阳性符合临床诊断，密切接触者和正常人的抗体阳性数较低，提示可能不存在隐性感染。     

人染色体11p15.5 BWS致病位点新基因C11orf21的初步功能分析

目的研究人染色体11p15.5Beckwith-Wiedemann综合征致病位点新基因C11orf21的生物学功能。方法用RT-PCR和Northern印记方法分析C11orf21基因的表达;研究C11orf21蛋白功能用Western印记和细胞培养方法。结果检测到C11orf21基因在成人和胎儿心脏和肝脏等组织转录,在心脏有较强的表达并有0.9和3.1kb两个转录物。C11orf21蛋白在COS-1和Hela细胞细胞质表达,蛋白相对分子质量为14kDa。结论初步分析显示C11orf21是11p15.5Beckwith-Wiedemann综合征致病位点的一个非印记基因,在成人心脏有较强表达的局限细胞质蛋白。     

LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters

Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features.     

Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome

Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A-->G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with non-consanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T-->G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T-->G mutation may be a common mutation.     

SARS冠状病毒的病原生物学分析及其启示

Severe acute respiratory syndrome (SARS) is the first new epidemic of the twenty - first century. A novel coronavirus (SARS - CoV) has been identified as the causative agent of SAP, S. The genome of SARS - CoV has 29,727 nucleatides in length. The genome organization, with 11 open reading flames, is similar to that of conronaviruses.Phylogenetic analyses and sequence comparisons showed that SARS- CoV is not closely related to any of the known coronaviruses, indicating neither a mutant nor recombinant of well -characterized coronaviruses. It is a complete new coronavirus from nonhuman hostPathological studies show that severe immune response, associated to cytokine dysregulation, may be related to the lung damage of fatal SRAS. Recombination of genomes of wild - type strains with vaccine coronavirus is a potential risk associated with the application of living attenuated coronavirus vaccines. The proteinases, controlling the activities of the SARS- CoV replication, and spike protein, involved in viral entry and pathogenesis, represent attractive targets of anti- SARS drug development. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates suggests a remarkable genetic conservation of the virus. Anti - SARS vaccine and drug development will benefit from this genetic conservation. SARS-CoV is not likely to change rapidly and thus may not readily mutate to a benign infection. The progress in anti - SARS research has been impressive. However, one of the most effective tools in the control of the SARS is quickly tracing and isolating the contacts of stricken patients before they spread the virus further.     

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome. Received: March 4, 2002 / Accepted: July 7, 2002     

Frontonasal dysplasia in the Klippel-Feil syndrome: A new associated malformation

This paper describes an 8-year-old girl with Klippel-Feil syndrome (KFS) associated with frontonasal dysplasia, Sprengel deformity and postaxial polydactyly. These findings are tentatively explained on the basis of a single mutant gene for KFS with broad action in the morphogenesis of the skeletal system.     

脑转移瘤同期加量混合调强放疗与调强放疗的剂量学比较

目的:探讨同时运用三维适形与调强的混合调强放疗（Hybrid-IMRT）与调强放疗（IMRT）用于脑转移瘤同期加量的剂量学差异。方法:选取20例进行头颅放疗的患者，分别设计Hybrid-IMRT计划和IMRT计划。Hybrid-IMRT计划包括全脑行三维适形（两野对穿）3 600 cGy/20 F、脑转移灶行IMRT同期加量至5 000 cGy/20 F；IMRT计划全程运用IMRT给予全脑照射3 600 cGy/20 F、脑转移灶5 000 cGy/20 F。在满足临床要求的前提下，比较两组计划靶区的均匀性指数、适形度指数、平均剂量和机器跳数，危及器官脑干、视神经、晶体、视交叉、眼球的最大剂量和平均剂量。结果:两种计划均能满足临床要求。Hybrid-IMRT计划的PGTV均匀性优于IMRT计划（P<0.001）；Hybrid-IMRT计划的脑干、视交叉、左右晶体的最大剂量与平均剂量，左右眼球的平均剂量以及左右视神经的最大剂量均低于IMRT计划（P<0.05）；Hybrid-IMRT计划的机器跳数比IMRT计划减少了约70%（P<0.001）。结论:两种计划均能满足临床要求，Hybrid-IMRT计划相较IMRT计划靶区剂量更加均匀，治疗时间缩短，也能更好地保护危及器官。     

3D facial morphometry in Italian patients affected by Aicardi syndrome

Aicardi syndrome (AIC) is a rare congenital neurodevelopmental disorder of unknown etiology, that affects almost exclusively females, originally characterized by corpus callosum agenesis, chorioretinal lacunae, and infantile spasms. The current diagnostic criteria also include qualitative facial features (prominent premaxilla, upturned nasal tip, decreased nasal bridge angle, sparse lateral eyebrows, and microphthalmia) that still need quantification. A three‐dimensional (3D) photogrammetric assessment of 11 Italian females, age 7–32 years, who satisfied AIC criteria, was performed. Linear distances and angles were computed from soft‐tissue facial landmarks coordinates. The z‐score values were calculated using data of 850 healthy reference females matched for age and compared by Mann–Whitney test (p < .01). Patients showed a shorter philtrum and right side orbital height (mean z‐scores: ?1.7, ?0.9), shorter superior, middle, and inferior facial depths (mean z‐scores: ?1.3, ?2.2, ?2.3), and a smaller length of mandibular ramus (mean z‐score: ?2.1); conversely, they showed larger nasal and lower facial widths, and lower facial convexity (mean z‐scores: 1.7, 1.4, 2.4). The inclinations of the orbit versus the true horizontal were increased bilaterally (mean z‐scores: 1.8, 1.1). Some common facial abnormalities were quantified in AIC patients using a noninvasive instrument. They may help clinicians in performing a definite AIC diagnosis in atypical or doubt cases.