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91.
Shannon G. Farmakis Ann M. Barnes John C. Carey Stephen R. Braddock 《American journal of medical genetics. Part A》2019,179(3):455-466
The purpose of this study was to determine whether trisomy 18 patients are at an increased risk of tumor development and require formal tumor screening recommendations. A literature search of trisomy 18 patients with reports of tumors or malignancies, and compilation of all previously reported as well as new unreported cases was performed. 67 patients with trisomy 18 were found to have documented malignancies. 44 patients had hepatoblastomas, 21 patients had Wilms tumors, one patient had a functional neurogenic neoplasia, and one patient had Hodgkins lymphoma. The increasing numbers of reported malignancies in patients with trisomy 18 supports the indication for an early screening process. Specific screening recommendations are outlined consisting of imaging exams and laboratory values performed at specific intervals. 相似文献
92.
Rachel Rabin Yoel Hirsch Martin M. Johansson Joseph Ekstein David A. Zeevi Beth Keena Elaine H. Zackai John Pappas 《American journal of medical genetics. Part A》2019,179(10):2144-2151
Warsaw breakage syndrome (WABS), caused by bi‐allelic variants in the DDX11 gene, is a rare cohesinopathy characterized by pre‐ and postnatal growth retardation, microcephaly, intellectual disability, facial dysmorphia, and sensorineural hearing loss due to cochlear hypoplasia. The DDX11 gene codes for an iron–sulfur DNA helicase in the Superfamily 2 helicases and plays an important role in genomic stability and maintenance. Fourteen individuals with WABS have been previously reported in the medical literature. Affected individuals have been of various ethnic backgrounds with different pathogenic variants. We report two unrelated individuals of Ashkenazi Jewish descent affected with WABS, who are homozygous for the c.1763‐1G>C variant in the DDX11 gene. Their phenotype is consistent with previously reported individuals. RNA studies showed that this variant causes an alternative splice acceptor site leading to a frameshift in the open reading frame. Carrier screening of the c.1763‐1G>C variant in the Jewish population revealed a high carrier frequency of 1 in 68 in the Ashkenazi Jewish population. Due to the high carrier frequency and the low number of affected individuals, we hypothesize a high rate of miscarriage of homozygous fetuses and/or subfertility for carrier couples. If the carrier frequency is reproducible in additional Ashkenazi Jewish populations, we suggest including DDX11 to Ashkenazi Jewish carrier screening panels. 相似文献
93.
Cell culture-based transdominant genetic techniques provide new methods for discovering peptide/RNA modulators of cellular pathways. We applied this technology to isolate a peptide inhibitor of human rhinovirus. A green fluorescent protein (GFP)-scaffolded library of cDNA fragments was expressed in HeLa cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. A DNA clone, I421, increased cell survival in an HRV14 challenge assay from less than 0.5% to greater than 60%. It encodes a 53-amino-acid C-terminal extension of the GFP scaffold. Particular subclones of Hela cells expressing I421 (exemplified by I421dp3) show a delay in virus production and a 50-fold decrease in viral RNA levels at 6-8 h postinfection. HRV2, HRV14, and HRV16 show a dramatic decrease in plaque-forming ability on I421dp3 while Coxsackievirus B3 showed a small reduction. Levels of ICAM-1, the receptor for the main rhinovirus serotype, are not altered in I421dp3. 相似文献
94.
De Luca A Buccino A Gianni D Mangino M Giustini S Richetta A Divona L Calvieri S Mingarelli R Dallapiccola B 《Human mutation》2003,21(2):171-172
The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. The majority of these mutations are private and rare, generating elevated allelic diversity with a restricted number of recurrent mutations. In this study, we have assessed the efficacy of denaturing high-performance liquid chromatography (DHPLC), for detecting mutation in the NF1 gene. DHPLC is a fast and highly sensitive technique based on the detection of heteroduplexes in PCR products by ion pair reverse-phase HPLC under partially denaturing conditions. We established theoretical conditions for DHPLC analysis of all coding exons and splice junctions of the NF1 gene using the WAVEmaker software version 4.1.40 and screened for mutations a panel of 40 unrelated NF1 patients (25 sporadic and 15 familial), genetically uncharacterized. Disruptive mutations were identified in 29 individuals with an overall mutation detection rate of 72.5%. The mutations included eight deletions (exons 4b, 7, 10a, 14, 26, and 31), one insertion (exon 8), nine nonsense mutation (exons 10a, 13, 23.1, 27a, 29, 31, and 36), six missense mutations (exons 15, 16, 17, 24, and 31), four splice errors (exons 11, 14, 36, and 40) and a complex rearrangement within exon 16. Eighteen (62%) of the identified disruptive mutations are novel. Seven unclassified and three previously reported polymorphisms were also detected. None of the missense mutations identified in this study were found after screening of 150 controls. Our results suggest that DHPLC provides an accurate method for the rapid identification of NF1 mutations. 相似文献
95.
A. Rottenstreich S. Benenson G. Levin G. Kleinstern A.E. Moses S. Amit 《Clinical microbiology and infection》2019,25(2):251.e1-251.e4
Objectives
To investigate the incidence, risk factors, clinical course and outcomes of pregnancy-related group A streptococcus (GAS) infection.Methods
A retrospective 13-year cohort study of culture-proven pregnancy-related GAS infection was performed at two university hospitals serving heterogeneous, multicultural, urban and rural populations.Results
Of 124 women diagnosed with pregnancy-related GAS infection, 115 (93%) were in the puerperium, an incidence of 0.8 cases per 1000 live births (95% confidence interval, 0.7–0.9). A multivariate analysis showed primiparity and cesarean delivery to be independent protective factors against puerperal GAS infection (adjusted odds ratios (95% confidence interval), 0.60 (0.38, 0.97) and 0.44 (0.23, 0.81), respectively). Of the nine remaining patients, eight were diagnosed after first trimester abortions and one had an infected ectopic pregnancy. Among the entire cohort (n = 124), the predominant manifestations were fever and abdominal tenderness. Twenty-eight patients (23%) had severe GAS infections. All were treated with β-lactams, and most (n = 104, 84%) received clindamycin. Only four (3%) required surgical intervention; the rest fully recovered with conservative medical treatment including antibiotics. No recurrences, maternal deaths or neonatal complications were noted.Conclusions
Pregnancy-related GAS infection is not rare; it lacks specific signs and still carries significant morbidity. Primiparity, a presumable surrogate for diminished exposure to children and thus less GAS carriage, and cesarean delivery in which perioperative antibiotic prophylaxis was uniformly provided, appear as protective factors against puerperal GAS infection. This hints to the importance of community-acquired GAS and may support shifting efforts from infection-control–oriented nosocomial investigations to screening and prevention–driven policies. 相似文献96.
97.
Nisselle AE Delatycki MB Collins V Metcalfe S Aitken MA du Sart D Halliday J Macciocca I Wakefield A Hill V Gason A Warner B Calabro V Williamson R Allen KJ 《Clinical genetics》2004,65(5):358-367
There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace. 相似文献
98.
Two novel mutations of the β-hexosaminidase α subunit gene were identified in Japanese patients with the infantile form of
Tay-Sachs disease. One mutation was a one-base deletion at nt613C, which generated a stop codon at two codons downstream,
in three unrelated patients. The other mutation was a one-base substitution of G-to-A at IVS 5, +1, which caused a splicing
abnormality, in one patient. A missense mutation of R170W, which has already been reported in other ethnic groups, was also
newly identified in one patient. In 1993, the most common mutation (IVS 5, −1G → T) in Japanese patients with Tay-Sachs disease
was reported as the major mutation in Japan accounting for 80% of 56 mutant alleles from 28 unrelated patients. The deletion
of nt613C was the second most common mutation, accounting for 5% of the mutant alleles. The previously reported mutation IVS
5, −1G → T and the nt613C deletion found in this study together accounted for 85% of the mutations causing Tay-Sachs disease
among Japanese. Since these two mutations were located in or close to exon 6 and since they abolish Fok I (IVS 5, −1G → T) and Sfa NI (nt613C deletion) restriction sites, respectively, they were screened rapidly by single polymerase chain reaction followed
by digestion with these enzymes.
Received: November 10, 1998 / Accepted November 14, 1998 相似文献
99.
《European journal of medical genetics》2021,64(12):104369
Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting. 相似文献
100.
Weber B. H. F. Stöhr H. Siedlaczck I. Longmire J. L. Deaven L. L. Duncan A. M. V. Riess O. 《Chromosome research》1994,2(3):201-207
A cosmid library specific for human chromosome 11 has been constructed from flow-sorted chromosomes. The flow-purified chromosomes were prepared from the hamster/human hybrid line J1 which contains chromosome 11 as the only human chromosome. Individual clones were sampled in 187 microtitre plates, resulting in a total of 17 952 colonies. Hybridization analysis revealed that 83.7% of these clones were of human and 10.4% of hamster origin. The average insert size was estimated at 33.6 kb, and only 2.4% of insert fragments appear to be rearranged. This should result in 494 487 kb of cloned human DNA representing 3.5 chromosome 11 equivalents. We have prepared high-density nylon membranes of the arrayed library containing 1 536 single colonies per filter. We have demonstrated the usefulness of the library in the molecular genetic analysis of human chromosome 11 by testing for the presence of possibly polymorphic simple repeat motifs, by identifying cosmids that contain inserts from the telomeric ends of chromosome 11 and by assessing the potential of the library for rapid chromosome walking. 相似文献