A survey of externally recognizable genitourinary anomalies in Korean newborns. Korean Urological Association

To estimate the incidence of externally recognizable genitourinary anomalies and associated anomalies in the newborns in Korea, retrospective and prospective studies have been performed. Thirty eight of 48 urology training hospitals participated in this nationwide survey. In this study we have included minor defects or variations in the anomaly to evaluate the incidence of the recognizable genitourinary conditions in the newborns. The incidence of genitourinary anomaly in 1,000 newborn delivery in a year was 11.0 in the prospective study and this figure is about three times higher than the retrospective study and is considered to be close to the true incidence. The incidence of genitourinary anomaly in 1,000 male newborn was 20.4. Hydrocele, cryptorchidism and hypospadias were most commonly observed. The incidence of hydrocele in 1,000 male newborn was 9.89 and the incidence of cryptorchidism was 7.26 and the incidence of hypospadias was 2.13. The incidence of associated anomaly in 100 genitourinary anomaly was 7.9. Congenital heart diseases and anorectal anomalies were commonly associated anomalies. In the newborns with genitourinary anomalies, premature infants account larger portion than is usually reported in total delivery.     

Minor physical anomalies in mentally healthy subjects: Internal consistency of the Waldrop Physical Anomaly Scale

The aim of the study was to investigate the prevalence of minor physical anomalies in mentally healthy subjects by using the Waldrop Physical Anomaly Scale and to assess the reliability (internal consistency) of the scale. The subjects were 82 mentally healthy individuals (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. Mentally healthy individuals show a low mean score of minor physical anomalies. The anomalies prevail in the craniofacial region. The correlations between the anomalies are low, which implies poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development and adversity. Providing a base for comparative studies of developmental disorders, the findings infer the necessity of a more reliable scale for examination of informative morphogenetic variants which can distinguish between minor malformations and phenogenetic variants and suggest the period of prenatal adversity. Am. J. Hum. Biol. 15:61–67, 2003. © 2002 Wiley‐Liss, Inc.     

Fra(2) (q13) and inv(9) (p11q12) in autism: causal relationship?

Twenty individuals with autism or related disorders underwent chromosome analysis and physical examinations with documentation of minor anomalies. Chromosome anomalies were identified in 3: 2 had the heritable folate sensitive fra(2) (q13) site and 1 had an inv(9) (p11q12). No heritable chromosome variants or anomalies were seen in 20 age and sex-matched control individuals. When patients with the fra(2) were excluded from analyses, there was no difference in the frequency of chromosome breaks and/or gaps between the study group and control group. The results of this study suggest that heritable folate sensitive fragile sites and other chromosome variants may be more commonly seen in individuals with autism or related disorders in childhood than in the general population.     

Surgey of tick-borne arboviruses in the Central African Republic (1973-1974). Isolation of Dugbe, CHF/Congo, Jos and Bhanja viruses]

As a complement of the study of the epidemiology of the arboviruses in Central Africa a survey of tick borne viruses has been done, in the Central African Republic, from December 1972 to June 1974; 15.103 ticks were collected, mainly from cattle at the slaughterhouses. They include: 10.085 Ambylomma variegatum, 4.113 Boophilus, 542 Rhipicephalus and 363 Hyalomma. From 892 monospecific pools inoculated into baby mice, 98 isolates of virus were obtained. Among the 57 isolates which have been fully identified (the identification of 41 other isolates is still in progress), 4 different serotypes of arbovirus have been found: Dugbe virus has been the most frequently found with 45 isolates from A. variegatum and I from B. decoloratus; this virus, previously isolated from human cases in Central African Republic in 1967 and 1970 has been isolated from a new human case in 1973. One isolate of CHF/Congo virus has been obtained from Hyalomma nitidum, but this virus has not yet been isolated from human beeings in C.A.R. The two other tick borne viruses isolated during this survey are Jos virus (9 isolates) and Bhanja virus (I isolate), all of them from A variegatum.     

HLA class II polymorphism in Aka Pygmies and Bantu Congolese and a reassessment of HLA-DRB1 African diversity

HLA-DRB1, -DQB1 and -DPB1 polymorphisms were investigated in two African populations, the Basse Lobaye Aka Pygmies of the Central African Republic, and a Bantu-speaking group from the Democratic Republic of Congo Kinshasa. Allelic and haplotypic frequency distributions reveal marked differences between the two populations in spite of their geographical proximity: the Aka exhibit high frequencies for several alleles, especially at the DPB1 locus (0.695 for DPB1*0402), probably due to rapid genetic drift, while the Bantu distributions are more even. Genetic distances computed from DRB1 allelic frequencies among 21 populations from North and sub-Saharan Africa were applied to a multidimensional scaling analysis. African populations genetic structure is significantly shaped by linguistic differentiation, as confirmed by an analysis of molecular variance. However, selective neutrality tests indicate that many African populations exhibit an excess of heterozygotes for DRB1, which is likely to explain the genetic similarity observed between some North African and Bantu populations. Overall, this study shows that natural selection must be taken into account when interpreting the patterns of HLA diversity, but that this effect is probably minor in relation to the stochastic events of human population differentiations.     

Phenotypic abnormalities: terminology and classification

Clinical morphology has proved essential for the successful delineation of hundreds of syndromes and as a powerful instrument for detecting (candidate) genes (Gorlin et al. [2001]; Syndromes of the Head and Neck; Oxford: Oxford University Press. 1 p]. The major approach to reach this has been careful clinical evaluations of patients, focused on congenital anomalies. A similar careful physical examination performed in patients, who have been treated for childhood cancer, may allow detection of concurrent patterns of anomalies and provide clues for causative genes. In the past, several studies were performed describing the prevalence of anomalies in patients with cancer. However, in most studies, it was not possible to indicate the biologic relevance of the recorded anomalies, or to judge their relative importance. Are the detected anomalies common variants, and should they thus be regarded as normal, or are they minor anomalies or true abnormalities, indicating a possible developmental cause? Classification of items in the categories of common variants (disturbances of phenogenesis with a prevalence >4%), minor anomalies (disturbances of phenogenesis with a prevalence 相似文献   

Novel mosaic TRAF7 likely pathogenic variant in an African American family

Pathogenic variants in TRAF7 are often de novo and features of individuals harboring these variants are characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features. We present a familial case in two African American patients with a novel, likely pathogenic c.1936G>A variant in TRAF7. Patient 1 is a 31-year-old female with a patent ductus arteriosus (PDA), intellectual disability, ptosis, and other dysmorphic features. She was identified to harbor this likely pathogenic variant in a mosaic (33.89%) state in leukocytes. Her son, Patient 2, is a 10-month-old male with a PDA, atrial septal defect, ptosis, developmental delay, history of feeding difficulties, congenital maxillary frenulum, and malrotation of the intestine. He has the same variant in a non-mosaic state. These cases demonstrate the variable expressivity observed with variants in TRAF7 within the same family and expand upon current understanding of mosaic TRAF7 variants. They also provide phenotypic data on genetic variation in individuals with African American ancestry, a population who has been underrepresented in the literature and may be less frequently referred to genetic specialists.     

Prevalence of congenital cytomegalovirus infection in Slovenia: a study on 2,841 newborns

Human cytomegalovirus (CMV) is the most frequent cause of congenital infection in humans. In the first prevalence study of congenital CMV infection in Eastern and Central Europe, all neonates born in a 22‐month period in two Slovenian maternity units (total of 2,841 newborns) were screened prospectively for congenital CMV infection by a real‐time polymerase chain reaction (PCR) in urine. In all newborns with positive screening results, plasma and dried blood spots (DBS) collected at birth were tested additionally for CMV DNA. Congenital CMV infection was confirmed by virus isolation from a urine sample collected within the first 2 weeks of life. Congenital CMV infection was identified in four out of 2,841 newborns tested (incidence 0.14%; 95% CI, 0.05–0.39%). In four newborns with confirmed congenital infection, the concentration of CMV DNA in urine ranged from 4.68 to 8.18 log₁₀ copies/ml, all four newborns had detectable CMV DNA in plasma taken at birth (1.26–3.34 log₁₀ copies/ml) and two out of four had detectable CMV DNA in DBS collected during newborn metabolic screening. None of the four newborns with confirmed congenital CMV infection was symptomatic. The study showed that the prevalence of congenital CMV infection at birth in Slovenia is among the lowest in the world and that CMV DNA PCR testing of urine is a suitable and affordable real‐time screening strategy for congenital CMV infection. If it is performed in 24 mini‐pools, the cost of screening is 1.4 €/newborn and the cost of detecting a single newborn with congenital CMV infection 1,000 €. J. Med. Virol. 84:109–115, 2011. © 2011 Wiley Periodicals, Inc.     

Rare genetic variants in cellular transporters,metabolic enzymes,and nuclear receptors can be important determinants of interindividual differences in drug response

PurposeIn this study we characterized the genetic variability of 146 clinically relevant genes influencing drug pharmacokinetics in African and European subpopulations, which are key determinants for interindividual variations in drug efficacy and adverse drug reactions.MethodsBy integrating data from the 1000 Genomes Project (n = 1,092 individuals) and the Exome Sequencing Project (ESP; n = 6,503 individuals), single-nucleotide variants (SNVs) were identified and analyzed regarding frequency, functional consequences, and ethnic diversity.ResultsIn total, we found 12,152 SNVs in exons, 312 of which were novel. The majority of variants were rare (minor allele frequency (MAF) <1%; 92.9%) and nonsynonymous (56.2%). We calculated that individuals of European and African descent harbor, on average, 100.8 and 121.4 variants across the 146 pharmacogenes studied, respectively. Additionally, by analyzing variation patterns across these populations, we pinpointed potential priority genes for population-adjusted genetic profiling strategies. Furthermore, we estimated, based on our variant frequency analyses, that approximately 30–40% of functional variability in pharmacogenes can be attributed to rare variants.ConclusionsOur results indicate that these clinically important genes are genetically highly variable and differ considerably between populations. Furthermore, the large extent of rare variants emphasizes the need for sequencing-based approaches and effective functionality predictions to allow for true personalized medicine.     

Night blindness, characteristic facies, and skeletal abnormalities in two brothers.

Two brothers are described with a similar physical appearance characterised by minor periorbital anomalies, malar flatness, a maxillary overbite, retrognathia, sloping shoulders, joint hyperextensibility, and minor radiological anomalies. In addition, they had a slowly progressing night blindness, myopia, and extinguished electroretinograms. The mother had mild expression of some of the physical anomalies and a decreased electroretinogram response to red light. We have been unable to find any report of similarly affected children. The possible modes of inheritance are discussed.     

Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants

Cervical cancer, mainly caused by infection with human papillomaviruses (HPVs), is a major public health problem in Mexico. During a study of the prevalence of HPV types in northeastern Mexico, we identified, as expected from worldwide comparisons, HPV-16, 18, 31, and 35 as highly prevalent. It is well known that the genomes of HPV types differ geographically because of evolution linked to ethnic groups separated in prehistoric times. As HPV intra-type variation results in pathogenic differences, we analyzed genomic sequences of Mexican variants of these four HPV types. Among 112 HPV-16 samples, 14 contained European and 98 American Indian (AA) variants. This ratio is unexpected as people of European ethnicity predominate in this part of Mexico. Among 15 HPV-18 samples, 13 contained European and 2 African variants, the latter possibly due to migration of Africans to the Caribbean coast of Mexico. We constructed phylogenetic trees of HPV-31 and 35 variants, which have never been studied. Forty-six HPV-31 isolates from Mexico, Europe, Africa, and the United States (US) contained a total of 35 nucleotide exchanges in a 428-bp segment, with maximal distances between any two variants of 16 bp (3.7%), similar to those between HPV-16 variants. The HPV-31 variants formed two branches, one apparently the European, the other one an African branch. The European branch contained 13 of 29 Mexican isolates, the African branch 16 Mexican isolates. These may represent the HPV-31 variants of American Indians, as a 55% prevalence of African variants in Mexico seems incomprehensible. Twenty-seven HPV-35 samples from Mexico, Europe, Africa, and the US contained 11 mutations in a 893-bp segment with maximal distances between any two variants of only 5 mutations (0.6%), including a characteristic 16-bp insertion/deletion. These HPV-35 variants formed several phylogenetic clusters rather than two- or three-branched trees as HPV-16, 18, and 31. An HPV-35 variant typical for American Indians was not identifiable. Our research suggests type specific patterns of evolution and spread of HPV-16, 18, 31, and 35 both before and after the worldwide migrations of the last four centuries. The high prevalence of highly carcinogenic HPV-16 AA variants, and the extensive diversity of HPV-18, 31, and 35 variants with unknown pathogenic properties raise the possibility that HPV intra-type variation contributes to the high cervical cancer burden in Mexico.     

Loop‐mediated isothermal amplification‐based diagnostic assay for monkeypox virus infections

Monkeypox virus (MPXV) causes a smallpox‐like disease in non‐human primates and humans. This infection is endemic to central and western Africa. MPXV is divided into two genetically different groups, Congo Basin and West African MPXV, with the former being the more virulent. A real‐time quantitative MPXV genome amplification system was developed for the diagnosis of MPXV infections using loop‐mediated isothermal amplification (LAMP) technology. Primers used for genome amplification of Congo Basin (C‐LAMP), West African (W‐LAMP), and both Congo Basin and West African (COM‐LAMP) MPXV by LAMP were designed according to the nucleotide sequences of the Congo Basin‐specific D14L gene, the West African‐specific partial ATI gene, and the partial ATI gene that is shared by both groups, respectively. The sensitivity and specificity of the LAMP were evaluated with nested PCR using peripheral blood and throat swab specimens collected from Congo Basin MPXV or West African MPXV‐infected monkeys. The sensitivity and specificity of COM‐LAMP, C‐LAMP, and W‐LAMP were 80% (45/56) and 100% (64/64); 79% (19/24) and 100% (24/24); and 72% (23/32) and 100% (40/40), respectively. The viremia level determined by LAMP assays increased with increases in the severity of the monkeypox‐associated symptoms. The newly developed LAMP assay was confirmed to be a rapid, quantifiable, and highly sensitive and specific system effective in the diagnosis of MPXV infections. The LAMP assays made it possible to discriminate between Congo Basin and West African MPXV. The LAMP developed in this study is useful not only for diagnosis of but also for the assessment of MPXV infections. J. Med. Virol. 81:1102–1108, 2009. © 2009 Wiley‐Liss, Inc.     

Normal values for morphological abnormalities in school children

Clinical morphology has proven to be a strong tool in the delineation of many syndromes and a helpful instrument in molecular studies. Numerous studies have been performed investigating the prevalence of minor anomalies in various disorders; all concluding that minor anomalies can well be utilized as indicators of altered embryonic differentiation. However, for adequate evaluation, normal values for phenotypic abnormalities are essential. So far, only few studies on the frequency of phenotypic abnormalities in the normal population have been done having one thing in common: all were performed in newborn infants. We studied morphological characteristics in a group of 1,007 school children, representative for the Dutch population, through a body surface examination using detailed definitions for all morphological findings. The region of study and distribution of children over various school types was chosen in such a way that it represented the general Dutch population. The median age of the studied children was 11 years (range 8-14 years), sex ratio (M:F) was 0.93. Nine hundred twenty-three children were of Caucasian descent, 84 others of mixed ethnic backgrounds. The reliability of the examinations was tested by independent scoring of 111 children by two observers, showing a kappa score of 0.85. Normal values for the morphological findings are presented together with their age-adjusted classification. These normal values provide a valuable source for validation of classifications of phenotypic abnormalities, especially those that are depending on frequency, that is, minor anomalies and common variants. Furthermore, they will allow a proper evaluation of patterns of phenotypic abnormalities found in patient groups with specific disorders.     

Identification of hepatitis B virus subgenotype A3 in rural Gabon

An hepatitis B virus (HBV) molecular survey was conducted in five remote villages in the equatorial forest in Gabon, Central Africa. Two hundred seventy out of 311 inhabitants (86.8%) were HBV-infected or had evidence of past HBV infection. Chronic hepatitis corresponding to hepatitis B surface antigen (HBsAg) positivity was suspected in 27 (8.6%) of the HBV-infected subjects. High HBV viral loads were detected mainly in children aged 4-7 years. The pre-S/S domains were sequenced in 13 cases and 12 strains belonged to HBV-A genotype. In one case we found evidence for recombination between genotypes A and E. Phylogenetic analysis revealed that Gabonese HBV strains were distinct from HBV-A subgenotypes (A1 and A2). These new HBV strains from Gabon clustered with previously reported HBV-A3 subgenotype strains from Cameroon and Democratic Republic of Congo. The analysis of the pre-S2 domain allowed us to determine two amino acid substitutions (N/152/S and N/174/T) specific to the Central African HBV-A3 subgenotype strains and one amino acid substitution (P/155/Q) unique to these new Gabonese HBV-A3 subgenotype isolates. Two full genome sequences of two new Gabonese HBV isolates are also presented and confirm the distinctive HBV-Gab-A3 cluster.     

HPA polymorphism in sub-Saharan African populations: Beninese, Cameroonians, Congolese, and Pygmies

The frequency of human platelet antigen-1 (HPA-1) to HPA-11w (excluding HPA-8w) and HPA-15 systems was studied in four sub-Saharan populations: Beninese, Congolese (Democratic Republic of Congo Kinshasa), Cameroonians, and Aka pygmies (Central African Republic). No report of HPA prevalence has previously been published concerning these populations which are characterized by the highest HPA-2b gene frequencies of any reported to date (Aka 0.393, Benin 0.292, Cameroon 0.237, and Congo 0.224) and at lesser degree HPA-5b (Aka 0.405, Congo 0.268, Cameroon 0.254, and Benin 0.182). This study is of great importance (i) particularly in the context of the diversity caused by the population migrations, we may observe today in our hospitals (ii) to confirm that the Pygmy population with distinctive frequencies (absence of the HPA-1b, HPA-2b, and HPA-5b highest frequencies) is an isolated population.     

新生儿耳廓形态学分型的初步研究

目的　初步了解东莞地区新生儿耳廓畸形的形态学分型及其发生率,获得新生儿耳廓测量数据。 方法 用人体测量仪对东莞厚街医院出生一周以内的321例新生儿两耳耳廓的长、宽等指标进行测量,并拍摄照片。根据耳廓畸形诊断标准,判断形态学分型,得到各类型的发生率,两耳和性别间差异及耳廓测量数据。 结果 321例新生儿中存在8种耳廓畸形的形态学分型,分别是招风耳、杯状耳、垂耳、Stahl’s耳、环缩耳、Conchal Crus、耳轮畸形和复合畸形,其中招风耳发生率为3.74%,杯状耳2.18%,垂耳5.61%,Stahl’s耳2.49%, 环缩耳13.40%,Conchal Crus6.07 %,耳轮畸形5.92 %,复合畸形4.05%。右耳Conchal Crus发生率较高,女婴耳轮畸形发生率较高。 结论 新生儿耳廓畸形发生率较高,国内外耳廓畸形分型诊断存在差异,需要开展多中心合作研究来确定中国新生儿耳廓畸形定量化诊断。     

Haplotypes bearing HLA-A, -B, and -DR: Bf and C4 genes in rheumatoid arthritis families

We have compared haplotypes bearing HLA-A, -B, -DR; Bf and C4 genes in 54 rheumatoid arthritis (RA) and 24 control families. There was no statistically significant differences in C4A or C4B gene frequencies between RA and control groups, although there were trends for C4B*Q0 to be reduced and C4B2 to be increased in DR4 positive RA compared with DR4 positive controls. The lack of any strong association between C4 variants and RA overall makes it unlikely that the association between RA and genes within the MHS represents a direct effect of variants within the C4A or C4B loci themselves. On comparison of DR4-bearing haplotypes, the haplotype B15-BfS-DR4 was increased fourfold and the B44-Bfs-DR4 haplotype was less frequent in the RA group. When C4 variants were also considered, the haplotype B44-C4B*Q0-C4A3-BfS-DR4 was nine times less frequent in RA patients than in controls. The observation that different DR4 bearing haplotypes may confer either increased or decreased susceptibility to RA suggests either that it is unlikely that DR4 itself is involved in the disease process or that specific haplotypic combinations are important. Thirty-two RA patients were HLA-DR4 negative. No single DR4 negative haplotype was found to confer significantly increased susceptibility to RA.     

Isolation of Thogoto virus from Amblyomma and Boophilus ticks in Central Africa]

A survey has been carried out in the Cameroons and the Central African Republic about the role of the ticks in the ecology of arboviruses in Central Africa. Attempts for virus isolation were made for 12,678 Amblyomma variegatum, 3,276 Boophilus decoloratus and 1,769 Boophilus annulatus, by inoculation into suckling mice. From 968 pools which were inoculated, 20 yielded isolates which were identified to Thogoto virus. Considering previously published results concerning tick-borne virus isolations in the Central African Republic, it appears now that five arboviruses are present in the ticks in central Africa : Dugbe, Jos and Thogoto (in A. variegatum, B. decoloratus and B. annulatus), Bhanja (in A. variegatum) and Chf. Congo (in Hyalomma nitidum).     

HLA A, B, C and DR association with insulin-dependent diabetes in Martinique

HLA-A,B,C, and DR frequencies have been determined in 34 Coloured Martinican IDDM patients to establish the HLA and IDDM associations. HLA A3, B15, B18, Cw3 and DR4 antigens associations with IDDM are confirmed by this study. We found an increase of B21 similar to that found in Asiatic Indians. As in some African Black populations and in Cape coloured people, A1, B8, and DR3 are not increased in our population. We should point out that our patients' ages of onset were low, and that some studies have found DR4 association in young patients and DR3 in older ones. The protective role of DR2 is confirmed here. B35 and Cw4 negative associations have been found. We have observed that the antigens associated with IDDM are decreased in our control population, except DR4, and that the negative associated DR/ and Cw4 antigens are increased compared to the Continental French population. This corresponds with the low IDDM incidence in Blacks and Coloured people.