陕北地因临床遗传病调查研究

本文对陕北地区一个地区级医院、六个县级医院从1981～1990年十年间临床所见的遗传病作了调查分析。共查阅病历188，943份，其中遗传病23，418份，占总病历数的12．39%；男性遗传病13，800例，女性9．181例，男：女=1．5：1。以发病年龄看，婴幼儿多于青少年，青少年多于中老年；按年度计算，前5年明显少于后5年。共发现遗传病种类131种，其中单基因病67种、3563例，占遗传病例15．21%；多基因病48种，18482例，占遗传病例78．92%；染色体病16种，1373例，占遗传病例5．86%。从本资料可见，多基因病最多，而且随年度出现率增高。其次隐性遗传病和染色体病较多，这可能与陕北地区自然条件差和科学文化发展慢以及通婚圈小等有关。     

徐州市0—14岁儿童遗传病及先天畸形流行病学调查

目的：了解徐州市遗传病及先天畸形分布及患病率。方法：对徐州市98642人中的0－14儿童遗传病及先天畸形进行了流行病学调查。结果：共调查24212名0－14岁儿童，男15089名，女13123名，其中遗传病及先天畸形儿445例，男265例．女180例，总患病率15．77‰，男、女患病率分别为17．56‰、13．72‰，男、女患病率有显著性差异；城市儿童3703名，乡村儿童24509名，遗传病及先天畸形患儿各67例、对378例，患病率分别为18．09‰、15．42‰，城乡患病率差异无统计学意义。共发现遗传病及先天畸形72种，其中染色体病、羊基因病、多基因病及其他可能与遗传有关的疾病分S4占病例总数的1．5％、22．02％、68．09％、8．23％。结论：本次调查显示遗传病及先天畸形严重影响儿童素质，加强优生遗传咨询及产前诊断工作．降低遗传病及先天畸形儿的出生是一项紧迫任务。     

328例非特异性精神发育迟滞的隐性基因分析

采用分离分析和血缘分析方法，对山东省遗传病调查中发现的３２８个父母双方均正常的中、重度非特异性精神发育迟滞（ＮＳＭＲ）家系进行了分析。结果表明，多发家庭先证者的平均近婚系数显著高于一般群体，分离比接近０．２５。提示隐性基因在中、重度ＮＳＭＲ发生中起一定作用。在重度ＮＳＭＲ，散发病例占４０．７％，Ｘ连锁隐性遗传占９．１２％，常染色体隐性遗传占５０．１８％。常染色体隐性基因位点数的最小估计值为２４，各位点的平均基因频率为０．００３５，携带者总频率为１７．５４％；在中度ＮＳＭＲ，散发病例占６１．５％，Ｘ连锁隐性遗传占１１．５３％，常染色体隐性遗传占２６．９７％，常染色体隐性基因位点数的最小估计值为１３２，各位点的平均基因频率为０．００２１，携带者总额率为５４．９５％。     

167例高遗传风险新生儿染色体分析

本文对１６７例高遗传风险新生儿进行了染色体分析，检出染色体异常３８例，染色体异常检出率为２２．８％，其中染色体不平衡结构畸变３３例（８６．８％），平衡结构畸变５例（１３．２％）。染色体异常新生儿女性２１例，男性１７例，女性多于男性。在有先天愚型表型特征、父（母）为染色体平衡易位携带者及多发畸形新生儿中染色体异常检出率最高，分别为９２．６％、７５％和５０％。在已明确为多基因遗传病的新生儿中染色体异常检出率为零。在染色体三体型患儿母亲中，年令≥３５岁者９例（２５％），既往流产史者５例（１３．９％）。     

小儿智力低下570例病因分析及预防

本文对１９９０－１９９５年来我所遗传咨询的智力低下患儿５７０例进行病因分析和家系调查，结果显示，引起小儿智力低下的原因有单基因遗传病５３例，占９．２９％，多为常染色体隐性遗传病，再发风险高。一经确诊，建议其母不再生育。染色体病引起的智力低下６１例，占１０．７０％，引起智力低下的常见染色体疾病是２１三体综合征共５９例，另２例为９ｐ－综合征，对生育过一个染色体病患儿的夫妇应做细胞遗传学检查，以便检出平衡易位携带者。本组有孕期不良因素接触史和分娩时有不利因素者２４５例，占４２．９％，家系分析有３４个家系成员中有智力低下患者，说明遗传和环境因素都可能是引起智力低下的原因。     

临海地区病残儿中遗传性疾病21O例鉴定结果分析

目的分析临海市近3年来医学鉴定的病残儿所患遗传性疾病的种类、发病原因,探讨减少遗传病再发生的防治措施和对策。方法对我市2010～2012年32个街道申请病残儿医学鉴定的遗传病进行分类及病因分析。结果在申请医学鉴定的624例病残儿中有遗传性疾病210例,其中多基因遗传病165例（78．57％）、单基因遗传病36例（17．14％）,其中常染色体遗传病32例（15．24％）及X-连锁性遗传病4例（1．90％）,染色体病5例（2．38％）。结论病残儿中遗传性疾病比例高,种类复杂,应加强遗传咨询和出生缺陷干预来预防遗传性疾病的发生,减少遗传性病残儿的发生。     

优生技术鉴定中的异常病例分析

报道分析237例智低、先天性缺陷患儿的临床诊断，智低患几为135例，占57％。染色体病的发生主要以父母生殖细胞突变为主，而单基因与多基因遗传病的发生以家系遗传为主。在286例产前诊断对象中发现23例异常胎儿，采用综合判断方法，准确率高。     

762例遗传咨询人群的调查与研究

本课题是经过５年（１９８９－１９９３）时间，对遗传病的商发人群进行调查，调查结果在７６２例中确诊为遗传性疾病的有１７个病种共有１１０例，检出率为１４．４％，这１１０例有５例的家族中有近亲婚配关系，近亲婚配率占随机婚配的４．５％，在１１０例遗传性疾病中属染色体造成的遗传病占发病总数的４１．７％，神经管缺损占遗传总发病率的１０％，是在调查中发病率较高的病种，苯丙酮尿症有本次调查中虽然发病率较低，但属见     

特发性癫痫遗传方式的研究

目的为了探讨特发性癫痫（ＩＥＰ）的遗传方式。方法采用家系分析、多基因分析和分离分析的方法，对山东省遗传病群体调查中发现的２１０个ＩＥＰ家系进行了研究。结果ＩＥＰ不符合多基因遗传，而主要为常染色体隐体遗传。分离分析结果显示，Ｕ×Ｕ多发家庭组和Ｕ×Ａ家庭组可以接受常染色体隐性遗传的假设；部分Ｕ×Ｕ组的家庭可以接受常染色体隐性遗传的假设，但是大多数Ｕ×Ｕ组的家庭为散发病例，散发病例比例为７８．５％。结论散发病例和Ｕ×Ｕ（ｆ）家庭组可能存在遗传异质性，其原因有待进一步的研究。     

基层卫生保健中抑郁发作诊断治疗的初步调查

使用ＷＨＯ提供的基层卫生保健病人特征问卷（ＰＨＣＰＣＱ），调查了北京市某区级医院连续就诊的２００例病人，１２项精神症状调查结果显示，其中９人至少存在６项，使用ＩＣＤ－１０研究用抑郁发作诊断标准由专科医生重新诊断应为抑郁发作病例，占４．５％，而基层卫生保健医生病历记录中有诊断抑郁发作者仅１例，占０．５％，二者差异有显著性，表明一些抑郁症病人可能会被基层卫生保健医生漏诊；精神药物的使用调查结果显示，苯二氮类药物最多，共３２例（１６％），抗抑郁剂仅１例（０．５％）；结果提示，对基层卫生保健医生进行有关抑郁症诊断治疗方面的培训是十分必要的。     

69例小儿遗传病分析

本文报告小儿遗传咨询门诊及新生儿科确诊的遗传病:染色体病23例,其中核型异常16例,结构异常7例;常染色体显性遗传病11例,常染色体隐性遗传病28例;性连锁遗传病6例;血红蛋白异常1例,共计69例。常染色体遗传病占55％,染色体异常综合征占33％。常染色体病种类繁多,尽管发病率不高,但危害很大,给诊断带来困难。     

Evaluation of MYC and chromosome 8 copy number in breast carcinoma by interphase cytogenetics

We used fluorescence in situ hybridization (FISH) to determine MYC and chromosome 8 copy number on whole nuclear imprint preparations of 24 breast carcinomas, seven benign breast samples, and two phyllodes tumors. None of the benign tissues and neither of the phyllodes tumors demonstrated an increased copy number for MYC or chromosome 8, which was defined as greater than two signals in > 10% of nuclei. In contrast, 22 of 24 carcinomas demonstrated an increased MYC copy number. The modal numbers of MYC copies/nucleus were 0–2 in seven cases (29%), 3–5 in seven cases (29%), 6–9 in five cases (21%), and >9 in five cases (21%). An increased chromosome 8 copy number was observed in 21 of 22 carcinomas with MYC gain, and the modal number of signals/nucleus was either identical to (n = 14; 64%) or less than (n = 8; 36%) the number of MYC copies. The number of MYC copies correlated with cellular DNA content, as determined by using flow cytometry. In peridiploid tumors (DNA index 0.9–1.2; n = 7), the MYC copy numbers/nucleus were 0–2 in five cases and 3–5 in two cases. In contrast, the modal MYC copy numbers/nucleus among the 11 hyperdiploid tumors (DNA index 1.3–1.9) were 0–2 in one case, 3–5 in four cases, 6–9 in five cases, and >9 in one case. All three tetraploid/hypertetraploid carcinomas exhibited >9 MYC copies/nucleus. We conclude that an increased MYC copy number, as detected by using interphase cytogenetics, is extremely frequent in human breast carcinomas. However, in most cases, MYC gene duplication is probably secondary to polysomy of chromosome 8 and/or genomic endoreduplication (i.e., DNA aneuploidy). Genes Chromosom. Cancer 18:1–7, 1997. © 1997 Wiley-Liss, Inc.     

Epidemiologic import of tuberculosis cases whose isolates have similar but not identical IS6110 restriction fragment length polymorphism patterns

Isolates of Mycobacterium tuberculosis from patients with epidemiologic links frequently demonstrate identical IS6110 restriction fragment length polymorphism (RFLP) patterns (i.e., RFLP clustering) because they are infected with the same strain. Uncertainty arises with isolates that differ from one another by a few IS6110 hybridizing bands. During the period from 1 January 1996 to 31 December 1999, isolates from 585 tuberculosis (TB) cases were analyzed by RFLP, representing 98.2% of the 596 culture-positive TB cases reported in Arkansas during the study period. Of the 585 cases for which RFLP was available, 419 (71.6%) had an RFLP pattern with more than five copies of IS6110. Of the total 74 clusters, 48 comprised isolates with more than five copies of IS6110 and included 164 cases. Sixty-nine isolates with more than five copies of IS6110 comprising 16 clusters and 60 unique isolates were found to be similar to at least 1 other isolate (differing from it by one or two hybridizing bands). Among the 129 cases whose isolates were similar to other clustered or unique isolates, 16 cases were discovered with epidemiologic links: 14 (15.2%) were among the 92 cases with IS6110 RFLP patterns similar to those in clusters, and 2 (5.2%) were among the 37 unique cases that were similar to another unique case. The isolates from the epidemiologically linked patients shared common spoligotypes; all except one case shared common polymorphic GC-rich sequence (PGRS) patterns. Of the 129 patients whose isolates differed from another by one or two hybridizing IS6110 bands, 101 (78.3%) shared common spoligotypes and 87 (67.4%) shared common PGRS RFLP patterns.     

甘肃省113个行政村遗传病调查报告

目的探讨甘肃省农村遗传病的病种、分类、致病因素。方法制定遗传病调查表,用整群分层抽样调查法获得病例,把调查结果分类汇总统计分析。结果调查82645人,发现遗传病54种,患者1246人,总患病率为1.51%。结论智力低下、先天性聋哑、畸形指等六种遗传病是影响甘肃农村人口素质的主要疾病,不同性别及地域患病率均有显著性差异;近亲婚配、婚姻陋俗、国家相关政策及优生措施落实不到位是影响人口遗传素质的相关因素;提出了改善甘肃农村地区人口遗传素质的对策。     

Identification of five new mutations of PDS/SLC26A4 in Mediterranean families with hearing impairment

Pendred syndrome is an autosomal‐recessive disorder characterized by congenital sensorineural hearing loss combined with goiter. This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS/SLC26A4) has been mapped to chromosome 7q22‐q31 and encodes a chloride‐iodide transport protein. Mutations in this gene are also a cause of non‐syndromic autosomal recessive hearing impairment (DFNB4). We have analyzed the PDS/SLC26A4 gene in Spanish and Italian families and we have detected five new mutations (X871M, T132I, IVS1‐2A>G, Y556H and 406del5). © 2001 Wiley‐Liss, Inc.     

Mitotic stability of transforming DNA is determined by its chromosomal configuration in the fungus Cochliobolus heterostrophus

Summary Cochliobolus heterostrophus was transformed with a plasmid (pH1S) containing a bacterial gene (hygB), which confers resistance to the antibiotic hygromycin B when under control of an 838-bp fragment of promoter 1 from C. heterostrophus. The plasmid integrated at either homologous (52% single copy, 33% tandemly repeated copies) or ectopic (4% single copy, 11% tandemly repeated copies) sites on different chromosomes, resulting in four distinct configurations of integrated DNA. All four configurations were highly stable during mitotic growth; virtually no loss of integrated DNA was detected after five subcultures on nonselective medium or after seven cycles of pathogenesis on maize, the normal host of this fungus. However, deletion of integrated DNA was detected after eight or more disease cycles. The frequency of deletion depended on the configuration of the recombinant chromosome. A single copy of pH1S integrated at an homologous site was flanked by direct repeats of the target sequence and was least stable; up to 50% of the population lacked integrated DNA after 12 disease cycles. A single copy integrated at an ectopic site had no repeated DNA directly associated with it and was the most stable; no deletions were detected after 12 disease cycles. Tandemly repeated copies of pH1S integrated at either homologous or ectopic sites appeared to have intermediate stability; 2–18% of each population lost at least one copy after 12 disease cycles, although in no case were all copies deleted. Cytosine residues of integrated DNA were methylated during mitotic growth, but this had no apparent effect on the expression of hygB.     

Haplotype variation at the IBD5/SLC22A4 locus (5q31) in coeliac disease in the Irish population

In addition to the well-established association of coeliac disease (CD) with HLA-DQ (6p21) and possibly CTLA4 (2q33), there is considerable evidence for a susceptibility locus on chromosome 5q, which contains many potential candidates for inflammatory disease, including a cluster of cytokine genes in 5q31. CD cases and controls were genotyped for four single-nucleotide polymorphism (SNP) markers that together characterize >90% of the haplotype variation at the IBD5 locus encoding, among others, the SLC22A4 gene. IBD5 and SLC22A4 map to 5q31 and have recently been associated with Crohn's disease and rheumatoid arthritis. Haplotype frequencies do not differ significantly between CD cases and controls in the Irish population, and therefore the chromosome 5 CD susceptibility locus most likely lies elsewhere on 5q.     

Neutrophil oxidative metabolism in Down syndrome patients with congenital heart defects

Down syndrome (DS) occurs when an individual has three, rather than two, copies of the 21st chromosome. Cytosolic superoxide dismutase (SOD‐1) is encoded by a gene on chromosome 21 and thus, SOD‐1 activity is elevated in patients with DS. Forty percent of all cases with DS are associated with congenital heart defects (CHD). Although the contribution of SOD1 to disease phenotype is unknown, it is considered to be a “molecular marker” of the disease. It was hypothesized herein that the presence of CHD may alter the expression of SOD1 and oxidative metabolism in patients with DS. This hypothesis was tested via four experimental groups as follows: patients with DS without CHD, DS patients with CHD, CHD patients without DS and controls. Expression and activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), myeloperoxidase (MPO), and catalase (CAT) were determined in neutrophils from all experimental groups. Intracellular hydrogen peroxide concentration and superoxide release were also evaluated in neutrophils. A significant increase was observed in SOD and GPx amount and activity in patients with DS with and without CHD. No significant difference was found in the amount and activity of MPO and CAT among the different experimental groups. Intracellular hydrogen peroxide concentration was similar in all groups, whereas a prominent decrease was seen in superoxide release in cases with DS. Patients with DS with and without CHD showed no significant differences in any of the measured parameters. The data suggest that CHD observed in patients with DS does not result from altered redox metabolism associated with the disease. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.     

Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17: A New Group of Tauopathies

Frontotemporal dementia is a neurological disorder characterised by personality changes, deterioration of memory and executive functions as well as stereotypical behaviour. Sometimes a Parkinsonian syndrome is prominent. Several cases of frontotemporal dementia are hereditary and recently families have been identified where the disease is linked to chromosome 17q21–22. Although, there is clinical and neuropathological variability among and within families, they all consistently present a symptomathology that has led investigatores to name the disease "Frontotemporal Dementia and Parkinson-ismlinked to chromosome 17." Neuropathologically, these patients present with atrophy of frontal and temporal cortex as well as of basal ganglia and substantia nigra. In the majority of cases these features are accompanied by neuronal loss, gliosis and microtubule-associated protein tau deposits which can be present in both neurones and glial cells. The distribution, structural and biochemical characteristics of the tau deposits differentiate them from those present in Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy and Pick's disease. No (β-amyloid deposits are present. The clinical and neuropathological features of the disease in these families suggest that Frontotemporal Dementia and Parkinsonism linked to chromosome 17 is a distinct disorder. The presence of abundant tau deposits in the majority of these families define this disorder as a new tauopathy.     

Use of FISH to detect chromosomal translocations and deletions. Analysis of chromosome rearrangement in synovial sarcoma cells from paraffin-embedded specimens.

Retrospective cytogenetic analysis was performed on paraffin-embedded cells from five cases of synovial sarcoma to evaluate the frequency of the X;18 translocation characteristic of this tumor. Fluorescent in situ hybridization with DNA probes for the centromeres of chromosomes X and 18 was used with whole chromosome painting probes for X and 18. Translocation was inferred when there were only two X and 18 centromere signals but three painting probe signals of unequal size. On this basis it was possible to identify the t(X;18) in three cases. The fourth case was found to have extra copies of chromosome 18 without translocation, while the fifth case, the only one with a questionable diagnosis, had a normal chromosome pattern with a minor clone showing a translocated 18 but a normal X. Thus this study demonstrates the feasibility and value of using fluorescent in situ hybridization to detect chromosome rearrangements in archival tumor specimens.