Methylenetetrahydrofolate reductase thermolabile variant and oral clefts.

Folic acid can prevent neural tube defects; in some cases the mechanism is probably a correction of a metabolic defect caused by thermolabile methylenetetrahydrofolate reductase (MTHFR) found in increased frequency in cases. It is less clear whether folic acid can prevent oral clefts, in part because it is not known whether thermolabile MTHFR is more common in those with oral clefts. This study examined the prevalence of the mutation (677 C-->T) that causes thermolabile MTHFR in subjects with oral clefts from a national Irish support group, and an anonymous control group randomly selected from a neonatal screening program covering all births in Ireland. Eighty-three of 848 control subjects were homozygous (TT) thermolabile MTHFR (9.8%). This defect was almost three times as common in the 27 subjects (25.9%) with isolated cleft palate (odds ratio 3.23, 95% confidence interval 1.32 -7.86, P = 0. 02) and somewhat more common in the 66 subjects with cleft lip with or without cleft palate (15.2%, odds ratio 1.65, 95% confidence interval 0.81-3.35, P = 0.20). When the two groups with different etiologies were combined, the overall odds ratio was 2.06 (95% confidence interval 1.16-3.66, P = 0.02). In the Irish population homozygosity for the common folate-related polymorphism associated with thermolabile MTHFR is significantly more frequent in those with isolated cleft palate, and could be etiologically important. Am. J. Med. Genet. 86:71-74, 1999. Published 1999 Wiley-Liss, Inc.     

New study on the relationship between oral clefts and fetal loss

The sibships of 741 non-syndromic individuals with cleft lip with or without cleft palate (CL +/- P), those of 115 subjects with isolated cleft palate (CP), plus 2 series of controls of the same size were studied in a variety of ways. The 2 most significant findings were a) a higher fetal loss in the sibships of probands of the most frequently affected sex (CL +/- P: male; CP: female) and b) increased fetal mortality in the sibships with sporadic cases of CL +/- P when compared to that found in sibships with more than one affected. In general the results do not support the hypothesis of a causal relationship between fetal death and non-syndromic CL +/- P or CP.     

An epidemiological and genetic study of facial clefting in France. II Segregation analysis.

Familial transmission of cleft lip with or without cleft palate (CL(P] and isolated cleft palate (CP) was studied in two French samples of 458 CL(P) and 156 CP nuclear families, using the recently implemented unified model. In neither case could discrimination be achieved between polygenic inheritance and monogenic inheritance with a high proportion of sporadic cases. In this type of disorder with a complex genetic basis the information furnished by such an approach, which only considers the affected status, is discussed. Future investigations on the joint familial transmission of the disease and different marker systems may help to identify the genes involved in these developmental anomalies.     

Epidemiological and phylogenic study of human metapneumovirus infections during three consecutive outbreaks in Normandy, France

Human metapneumovirus (hMPV) is responsible for respiratory tract disease, particularly in the young and elderly population. An epidemiological and phylogenic study was performed on children admitted to hospital with an acute lower respiratory tract infection (LRI). Data were obtained and analyzed over three consecutive winters, from 2002-2003 to 2004-2005. Each year during the winter period, from November to March, 2,415 nasal swabs were tested by a direct immunofluorescence assay (DFA) for influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses, and adenoviruses. Rhinoviruses, enteroviruses, and coronaviruses OC43 and 229E were detected by RT-PCR. A RT-PCR designed for the M gene was performed on negative samples for hMPV detection and phylogenic analyses. For the three consecutive winters, hMPV represented 10%, 22.6%, and 8.8% of virus-negative samples, respectively. In most cases, clinical symptoms indicated a LRI with a final diagnosis of bronchiolitis. During the winter of 2003-2004, all viral clusters (A1, A2, B1, and B2) that circulated in France shifted progressively from the A group to the B group. This study determined the prevalence of hMPV in Normandy, its clinical impact and permitted the analysis of the molecular evolution during the successive outbreaks.     

An epidemiological and genetic study of facial clefting in France. I. Epidemiology and frequency in relatives.

The frequencies of cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) have been estimated in France to be 0.082% and 0.035%, respectively, after exclusion of malformation syndromes. A genetic and epidemiological study has been carried out on 468 patients with CL(P) and 163 with CP. The results are given in detail and some specific points are discussed: the apparently low incidence in France, the relationship between sex ratio and abortion rates, the maternal effects, and the possibility of an association between CL(P) and CP.     

Contribution of genomic copy-number variations in prenatal oral clefts: a multicenter cohort study

PurposeWe sought to investigate the utility of chromosomal microarray analysis (CMA) for prenatal diagnosis of oral clefts, as compared with traditional chromosome analysis, for improved prenatal genetic counseling and discovery of a potential correlation between genotype and oral cleft.MethodsThis retrospective analysis encompassed 270 prenatal oral cleft cases with documented detailed ultrasound findings and CMA results from four referral centers. Detection rates for pathogenic copy-number variants (CNVs) were calculated and compared with cases for which chromosome analysis was also performed.ResultsThe overall detection rate was 14.8% (40/270) for pathogenic CNVs by CMA, 7.2% (9/125) for the nonsyndromic cases, and 21.4% (31/145) for the syndromic cases. Of the nonsyndromic cases with ultrasound soft markers, 20% (5/25) were identified with pathogenic CNVs. CMA showed an improved detection rate of 15.3% (29/190) compared with 10.5% (20/190) for chromosome analysis.ConclusionThis study not only highlights the improved detection of chromosomal defects by CMA in prenatal oral clefts but also deepens our understanding of oral clefts. The results suggest that CMA is highly recommended in prenatal invasive genetic testing not only for syndromic oral cleft cases but also for nonsyndromic cases with soft markers. Candidate genes including CRKL, AKAP8, SYDE1, BRD4 are worthy of further investigation regarding their role in human palatogenesis.Genet Med 18 10, 1052–1055.     

湛江地区207例先天愚型的染色体分析

对湛江地区２０７例先天愚型进行了染色体分析，标准２１三体型占８８．４１％，易位型占３．８６％，嵌合型占６．７６％，伴有其它染色体异常者占０．９７％。对易位型和伴有其它染色体异常者作了家系分析。对先天愚型的细胞遗传学病因及先天愚型患病率的性别差异问题作了讨论     

Epidemiological study of tuberculosis in the area of Angers,France, as studied by 3 PCR-based fingerprinting methods

The new genotyping methods efficiently complement classical epidemiological investigation in order to attempt a global approach to TB control. In the present work, we have studied the genomic diversity of Mycobacterium tuberculosis isolated during the year 1998 within the district of Angers, France (260,000 inhabitants distributed in 29 districts), in order to identify recent transmission events and any related risk factors. The methods used included "spacer oligonucleotide typing" or spoligotyping, "variable number of DNA tandem repeats" or VNTR, and "double repetitive element PCR" or DRE-PCR. The resulting spoligotyping and VNTR results were also feeded to international databases and compared with >10,000 isolates for spoligotyping and 500 isolates for VNTR, representative of about 60 countries. The results obtained underlined that most of the TB cases in our setting probably reflected reactivation cases, as clustered cases indicative of potential events of recent transmission were rare. Furthermore, interrogation of international databases showed that most of the isolates from the Angers region belonged to major conserved families of TB isolates representative of Europe, with only rare cases of Asian origin, or those previously reported in specific epidemies reported from elsewhere.     

Challenges of preconception genetic testing in France: A qualitative study

Preconception genetic testing is carried out to inform couples on their carrier status for recessive or X-linked genetic disease, and aims to extend their possible reproductive choices. These genetic tests are available in several countries and are currently being considered in France in the context of bioethics laws revision, raising multiple medical, ethical, and societal concerns. To provide insights into questions relative to preconception genetic testing implementation, we conducted, through a qualitative research methodology, individual and group interviews in families with experience of genetic disease, physicians and researchers in the human and social sciences, and an ethics committee. In particular, the respondents agreed on the importance of a free test and an informed choice. The economic stakes of the test appeared to be a major determinant of its development for the participants. The use of genetic data has been a source of raised fears of a eugenic drift. The remaining questions were relative to the pathologies to be tested, the access to the test, its supervision, the role of physicians and in particular of primary care professionals. Based on individual opinions and collective debates, our work delimits the challenges of preconception genetic testing implementation in France through a qualitative methodology, providing further data necessary to its introduction in the health care system.     

Mitochondrial myopathy: a genetic study of 71 cases.

Of 71 index cases with histologically defined mitochondrial myopathy, 13 (18%) had relatives who were definitely affected with a similar disorder. Eight familial cases from four families were confined to a single generation. In five families maternal transmission to offspring occurred. There were no instances of paternal transmission, but one patient had an affected cousin in the paternal line. No consistent clinical syndrome or pattern of inheritance emerged for any identified defect of the mitochondrial respiratory chain, localised biochemically in 41 cases. Overall, the recurrence rate was 3% for sibs and 5.5% for offspring of index cases. Review of published reports of familial cases of mitochondrial myopathy suggests that the ratio of maternal to paternal transmission is about 9:1. We conclude that these disorders may be caused by mutations of either nuclear or mitochondrial genes.     

113例实验室确诊手足口病流行病学特征和临床特点分析

目的 了解不同病原类型以及普通、重症病例手足口病患儿的流行特征及临床特点.方法 采用描述流行病学方法对113例实验室确诊手足口病病例的流行病学特征和临床特点进行详细分析.结果 113例手足口病确诊病例流行特征与同期疫情流行特征基本相同,不同病原类型以及普通、重症病例手足口病部分临床特点存在差异.结论 应根据本病特点开展防控工作,早期识别重症病例,重点应做好暴发疫情的调查处置,减少重症和死亡病例.     

Regional analysis on the occurrence of oral clefts in South America

The aim of this work was to search for unequal birth prevalence rates (BPRs) of cleft lip +/- cleft palate (CL/P), and cleft palate only (CPO), among different geographic areas in South America, and to analyze phenotypic characteristics and associated risk factors in each identified cluster. Included were 5,128 CL/P cases, 1,745 CPO cases, and 3,712 controls (like-sexed, non-malformed liveborn infant, born immediately after a malformed one, in the same hospital), over 4,199,630 consecutive births. They were ascertained between 1967 and 2004, in 190 maternity hospitals of the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas) network, in 102 cities of all 10 South American countries. Non-predefined geographical areas with significantly unusual cleft BPRs were identified with Kulldorf and Nagarwalla's spatial scan statistic, employing number of cases and births, and exact location of each hospital. Expected values were cleft BPRs registered for the entire ECLAMC hospital network. Syndromic and non-syndromic clefts were considered for cluster analysis, and phenotypic characterization, while only non-syndromic for risk factor analysis. Seven clusters for CL/P, and four for CPO, with unusual BPRs were identified. CL/P cases in high BPR areas were more severe than elsewhere in the sample, similar to a previous ECLAMC report on microtia. For CL/P, high BPR clusters were associated with high altitude above sea level, Amerindian ancestry, and low socioeconomic strata; low BPR clusters showed association with African Black ancestry. Advanced maternal age, a recognized risk factor for CPO, was also associated with the only identified geographic cluster for CPO.     

T-cell lymphoma presenting in the breast: a histologic, immunophenotypic and molecular genetic study of four cases.

Primary non-Hodgkin's lymphoma of the breast is uncommon. Most primary breast lymphomas are of B-cell phenotype, with only rare cases showing a T-cell phenotype. In this study, we report the clinicopathologic features of four cases of T-cell lymphoma in the breast. The patients all were female with a mean age of 48 years (range, 13 to 77 years). All cases showed immunoreactivity in paraffin-embedded tissue for T-cell markers CD3, CD45RO, and CD43. beta F1 was positive in three of four cases. The four cases were further subclassified as anaplastic large cell lymphoma (CD30 positive) of T-immunophenotype; natural killer/T-cell lymphoma; peripheral T-cell (CD4 positive), large cell type; and peripheral T-cell (CD8 positive, T-cell intracellular antigen positive), medium cell type. Three of the four cases were monoclonal for T-cell receptor beta and/or T-cell receptor gamma. The one case of natural killer/T-cell lymphoma was negative for monoclonality with both T-cell receptor beta and gamma by molecular diagnostic studies. In all cases, IgH was negative. Follow-up was obtained in three cases. Two patients died within less than 1 year after the diagnosis. The third patient died within 18 months of the diagnosis. Our results suggest an aggressive clinical course for T-cell lymphomas that present in the breast.