ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

Associations of Cerebrovascular Metabolism Genotypes With Neuropsychiatric Symptoms and Age at Onset of Alzheimer's Disease Dementia

Objective: To study associations of cerebrovascular metabolism genotypes and haplotypes with age at Alzheimer’s disease dementia (AD) onset and with neuropsychiatric symptoms according to each dementia stage. Methods: Consecutive outpatients with late-onset AD were assessed for age at dementia onset and Neuropsychiatric Inventory scores according to Clinical Dementia Rating scores, apolipoprotein E gene (APOE) haplotypes, angiotensin-converting enzyme gene (ACE) variants rs1800764 and rs4291, low-density lipoprotein cholesterol receptor gene (LDLR) variants rs11669576 and rs5930, cholesteryl ester transfer protein gene (CETP) variants I422V and TaqIB, and liver X receptor beta gene (NR1H2) polymorphism rs2695121. Results: Considering 201 patients, only APOE-ɛ4 carriers had earlier dementia onset in multiple correlations, as well as less apathy, more delusions, and more aberrant motor behavior. Both ACE polymorphisms were associated with less intense frontally mediated behaviors. Regarding LDLR variants, carriers of the A allele of rs11669576 had less anxiety and more aberrant motor behavior, whereas carriers of the A allele of rs5930 had less delusions, less anxiety, more apathy, and more irritability. CETP variants that included G alleles of I422V and TaqIB were mostly associated with less intense frontally mediated behaviors, while severely impaired carriers of the T allele of rs2695121 had more anxiety and more aberrant motor behavior. Conclusion: Though only APOE haplotypes affected AD onset, cerebrovascular metabolism genotypes were associated with differences in several neuropsychiatric manifestations of AD.

Analysis of gene expression changes associated with human carcinoma-associated fibroblasts in non-small cell lung carcinoma

BACKGROUND: This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC). METHODS: We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis. RESULTS: We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-ß signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%. CONCLUSION: Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.

Chromosomal microarray analysis of 2000 pediatric cases / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the feasibility of chromosomal microarray analysis(CMA) for studying the correlation between birth defects and chromosomal aberrations.</p><p><b>METHODS</b>A total of 2000 patients with birth defects were recruited for the CMA testing.</p><p><b>RESULTS</b>Five hundred twenty two patients (26.1%) were found to have chromosomal abnormalities. These included 24 cases with numerical abnormalities, 11 with mosaicisms, and 11 with uniparental disomies. The remaining 476 cases were of well-known microdeletion or microduplication syndromes. The advantage of CMA over conventional karyotyping was demonstrated in many cases.</p><p><b>CONCLUSION</b>As a powerful tool for patients with birth defects, CMA can produce a higher diagnostic yield compared with conventional karyotyping.</p>

Three cases of rare SRY-negative 46,XX testicular disorder of sexual development with complete masculinization and a review of the literature

PURPOSE: To identify the clinical characteristics of SRY-negative male patients and genes related to male sex reversal, we performed a retrospective study using cases of 46,XX testicular disorders of sex development with a review of the literature. MATERIALS AND METHODS: SRY-negative cases of 46,XX testicular disorders of sex development referred for cytogenetic analysis from 1983 to 2013 were examined using clinical findings, seminal analyses, basal hormone profiles, conventional cytogenetic analysis and polymerase chain reaction. RESULTS: Chromosome analysis of cultured peripheral blood cells of 8,386 individuals found 19 cases (0.23%) with 46,XX testicular disorders of sex development. The SRY gene was confirmed to be absent in three of these 19 cases (15.8%). CONCLUSION: We report three rare cases of SRY-negative 46,XX testicular disorders of sex development. Genes on autosomes and the X chromosome that may have a role in sex determination were deduced through a literature review. These genes, through differences in gene dosage variation, may have a role in sex reversal in the absence of SRY.

Association of the deleted DAZ gene copy related to gr/gr and b2/b3 deletions with spermatogenic impairment / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of the deleted azoospermia (DAZ) gene copy related to gr/gr and b2/b3 deletions in the AZFc region with male spermatogenic impairment.</p><p><b>METHODS</b>This study included 121 infertile men with different de- grees of spermatogenic impairment and 95 healthy donors from the sperm bank. Using PCR, PCR-RFLP, and Y chromosome specific sequence tagged sites (STS) , we analyzed the association of DAZ gene copy deletions related to gr/gr and b2/b3 deletions in the AZFc region with spermatogenic impairment.</p><p><b>RESULTS</b>There were 15 cases of gr/gr deletion (12. 40% ) and 6 cases of b2/b3 deletion (4.96%) in the infertility group as compared with 13 cases of gr/gr deletion (13.68%) and 1 case of b2/b3 deletion (1.05%) in the control. Analysis of the DAZ-specific single nucleotide variant (SNV) loci revealed 11 gr/gr-DAZI/DAZ2 deletions (9.09%), 4 gr/gr-DAZ3/DAZ4 deletions (3.31%), and 6 b2/b3-DAZ1/DAZ2 deletions (4.96%) in the infertile men in comparison with 3 gr/ gr-DAZ1/DAZ2 deletions (3.16%), 10 gr/gr-DAZ3/DAZ4 deletions (10.53%), and 1 b2/b3- DAZ3/DAZ4 deletion (1.05%) in the control.</p><p><b>CONCLUSION</b>Partial deletions of gr/gr and b2/b3 exist in both healthy men and male patients with different degrees of spermatogenic impairment and cannot be considered as a risk factor for spermatogenesis impairment. However, deletions of different DAZ duplicons in gr/gr and b2/b3 deletions have different effects on spermatogenesis. DAZ1/DAZ2 instead of DAZ3/DAZ4 deletions might be associated with spermatogenesis impairment.</p>

Application of droplet digital PCR technology for genetic testing and prenatal diagnosis of spinal muscular atrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical application of droplet digital PCR (ddPCR) for genetic testing and prenatal diagnosis of spinal muscular atrophy (SMA) with deletion of SMN1 gene exon 7.</p><p><b>METHODS</b>A total of 138 clinical samples, including 121 peripheral blood, 13 amniotic fluid, 2 umbilical cord blood and 2 chorionic villi from 56 SMA families, were tested by both ddPCR and multiplex ligation-dependent probe amplification (MLPA). Results of the two approaches were analyzed with commercial software QuantaSoft (ddPCR) and Coffalyser (MLPA), respectively.</p><p><b>RESULTS</b>Among the 138 cases, 25 had two copies, 84 had one copy, and 29 had null copy of exon 7 of the SMN1 gene. The results of ddPCR and MLPA were completely consistent.</p><p><b>CONCLUSION</b>As a rapid, precise and economically efficient method, ddPCR will provide a new choice for genetic testing of SMA.</p>

Analysis of heterozygous duplication of PMP22 gene in a pedigree affected with Charcot Marie Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze mutation of the PMP22 gene in a pedigree affected with Charcot-Marie-Tooth disease.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of the proband and members from his family, and fetal DNA was extracted from amniotic fluid sample. Multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization (array-CGH) analyses were carried out to determine the copy number of the PMP22 gene. Sanger sequencing was carried out to detect point mutations of the PMP22 gene.</p><p><b>RESULTS</b>A heterozygous duplication of the PMP22 gene was detected in the proband and his father, while no point mutation, insertion or deletion was found in them. No duplication or deletion of the PMP22 gene was found in other family members.</p><p><b>CONCLUSION</b>Based on clinical symptoms and genetic findings, the heterozygous duplication of the PMP22 gene is probably the cause of the disease in the proband. The fact that the father has carried the same duplication but with no detectable symptom may be due to irregular transmission pattern of the mutation. Genetic counseling for the family should therefore be with caution.</p>

Advances in congenital vertebral malformation caused by genomic copy number variation / 中华外科杂志

Congenital vertebral malformation (CVM) is a congenital vertebral structural deformity caused by abnormal somitogenesis during embryonic development, of which the reason lies in gene mutation or abnormal regulation of the genes that coordinate somitogenesis during embryonic period. ICVAS had proposed a new classification algorithm for CVM, which facilitated exploration for its genetic etiology. Genomic Copy Number Variation (CNV) is a kind of DNA mutation, which is important for human evolution, phenotype polymorphism and diseases. Series of advances have been made on genetic causes of CVM, especially on CVM caused by CNV. CNVs of chromosome 16p11.2, 10q24.31, 17p11.2, 20p11, 22q11.2 and a few other regions are associated with CVM, indicating that gene dosage may play important roles in the development of the spinal cord.

Clinicopathological Implications of Mitochondrial Genome Alterations in Pediatric Acute Myeloid Leukemia

BACKGROUND: To the best of our knowledge, the association between pediatric AML and mitochondrial aberrations has not been studied. We investigated various mitochondrial aberrations in pediatric AML and evaluated their impact on clinical outcomes. METHODS: Sequencing, mitochondrial DNA (mtDNA) copy number determination, mtDNA 4,977-bp large deletion assessments, and gene scan analyses were performed on the bone marrow mononuclear cells of 55 pediatric AML patients and on the peripheral blood mononuclear cells of 55 normal controls. Changes in the mitochondrial mass, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were also examined. RESULTS: mtDNA copy numbers were about two-fold higher in pediatric AML cells than in controls (P<0.0001). Furthermore, a close relationship was found between mtDNA copy number tertiles and the risk of pediatric AML. Intracellular ROS levels, mitochondrial mass, and mitochondrial membrane potentials were all elevated in pediatric AML. The frequency of the mtDNA 4,977-bp large deletion was significantly higher (P< 0.01) in pediatric AML cells, and pediatric AML patients harboring high amount of mtDNA 4,977-bp deletions showed shorter overall survival and event-free survival rates, albeit without statistical significance. CONCLUSIONS: The present findings demonstrate an association between mitochondrial genome alterations and the risk of pediatric AML.

Research advances in candidate genes for autism spectrum disorder / 中国当代儿科杂志

Autism spectrum disorder (ASD) is a kind of neurodevelopmental multigenic disorder. More than one hundred of candidate genes for ASD have been reported. The candidate gene research for ASD involves in chromosome loci and screening of candidate genes and epigenetic abnormalities for candidate genes. The reported genes encode neural adhesion molecules, ion channels, scaffold proteins, protein kinases, receptor protein and carrier protein, signaling modulate molecules and circadian relevant proteins. The research of mutation screening and expression regulation of candidate genes can help to elucidate genetic mechanisms for ASD, and may provide new approaches for the diagnosis and treatment of this disorder. This article reviews the research advance in candidate genes for ASD.

[Association of Higher Defensin Beta-4 Genomic copy numbers with Behcet's Disease in Iraqi Patients]

Objectives: Behcet's disease [BD] is an immune-mediated small vessel systemic vasculitis. Human beta-defensins are antimicrobial peptides associated with many inflammatory diseases and are encoded by the beta-defensin family of multiple-copy genes. However, their role in BD necessitates further investigation. The aim of the present study was to investigate the possible association of BD in its various clinical forms with defensin beta-4 [DEFB4] genomic copy numbers

Methods: This case-control study was conducted from January to September 2011 and included 50 control subjects and 27 unrelated Iraqi BD patients registered at Baghdad Teaching Hospital, Bagdad, Iraq. Copy numbers of the DEFB4 gene were determined using the comparative cycle threshold method by duplex real-time polymerase chain reaction technology at the Department of Dermatology of Jena University Hospital, Jena, Germany

Results: DEFB4 genomic copy numbers were significantly higher in the BD group compared to the control group [P = 0.010]. However, no statistically significant association was found between copy numbers and clinical variables within the BD group

Conclusion: The DEFB4 copy number polymorphism may be associated with BD; however, it is not associated with different clinical manifestations of the disease

Investigação clínica e citogenética molecular em pacientes com atraso de desenvolvimento neuropsicomotor associado à malformação congênita / Clinical and molecular cytogenetics investigation in patients with psychomotor delay associated with congenital malformation

Introdução: Com a sofisticação das técnicas de análise do DNA, a medicina moderna tem à sua disposição boas possibilidades para elucidar quadros clínicos indefinidos em pacientes que possuem microrrearranjos cromossômicos complexos. O desenvolvimento da técnica de MLPA (Multiplex ligation-dependent probe amplification) aliado à tecnologia dos arrays (WGAS - whole genome array screening) possibilitou analisar de uma só vez, diferentes regiões de interesse clínico no genoma humano. Objetivo: O presente trabalho teve como objetivo estudar pacientes com atraso de desenvolvimento neuropsicomotor (ADNPM) associado à malformação congênita (MC) com cariótipo prévio normal ou inconclusivo. Material e métodos: Participaram do estudo 71 pacientes com ADNPM associado à MC que foram analisados utilizando o teste de MLPA com os kits P036 e P064, seguido de WGAS com as diferentes plataformas (Agilent, Affymetrix e Illumina). Resultados: Entre os 33 pacientes com alterações patogênicas e de significado clínico incerto (VOUS) encontramos: 12 pacientes com deleção, 5 com duplicação e 16 com duplicações e deleções (dup/del) concomitantes. Foram 29 pacientes com alterações patogênicas conclusivas, 4 pacientes com CNVs classificadas como VOUS e 15 pacientes tiveram resultado de array normal além dos outros 23 que apresentaram alterações benignas, ou por não apresentarem genes na região alterada, ou por serem genes sem fenótipos descritos, ou ainda, as alterações foram herdadas de genitores normais. Na casuística total foram encontrados 4 pacientes com regiões de perda de heterozigosidade. Conclusões: A utilização de uma estratégia combinada utilizando diferentes kits de MLPA, com capacidade para detectar as principais microalterações genômicas patogênicas conhecidas, associada à aplicação do WGAS possibilitou a detecção de alterações submicroscópicas, bem como a correlação clínica adequada para pacientes não diagnosticados pela citogenética clássica. Dessa forma,...

Introduction: The recent technological advances on DNA-based techniques have established in modern medicine good opportunities to elucidate undefined clinical cases in patients with complex chromosomal microrearrangements. The performance of MLPA (Multiplex ligation-dependent probe amplification) technique together with array technologies (WGAS - whole genome array screening) created the possibility of one single experiment to analyze different regions of interest in the human genome. Objective: Patients with psychomotor delay (PSMD) associated with multiple congenital anomalies who had normal or inconclusive G-band-karyotype (MCA) were studied in order to understand the genotype-phenotype correlations. Material and methods: This study involved 71 patients with psychomotor delay (PSMD) associated with multiple congenital anomalies (MCA) analyzed by MLPA (P036 and P064 kits), followed by WGAS different platforms (Agilent, Affymetrix e Illumina®). Results: Among 33 patients with pathogenic and uncertain (VOUS) copy number variations (CNV) were found: 12 deletions, 5 duplications and 16 concomitant duplication and deletion (dup/del). There were 29 patients with conclusive pathogenic findings, 4 patients with VOUS and 16 patients with normal array, but others 23 patients with benign results, which means there is no gene content in the region involved, or because these genes were not linked to phenotype, or even due to CNVs inherited of healthy parents. From the whole casuistic, 4 individuals presented loss of heterozygosity (LOH) regions. Conclusions: The use of a combined strategy of analysis (MLPA - WGAS) with a high capacity to detect pathogenic CNVs allows unraveling microscopic imbalances, and consequently, offers an adequate clinical correlation for patients not previously diagnosed by classical cytogenetics. In conclusion, this study suggests a new model for the combined application of these techniques, which represents an optimal alternative for a genomic...

Clinical Significance of MET Gene Copy Number in Patients with Curatively Resected Gastric Cancer / 전남의대학술지

The present study analyzed the prognostic impact of MET gene copy number in patients with curatively resected gastric cancer who received a combination regimen of cisplatin and S-1. The MET gene copy number was analyzed by use of quantitative real-time polymerase chain reaction. From January 2006 to July 2010, 70 tumor samples from 74 patients enrolled in a pilot study were analyzed. According to a cutoff MET gene copy number of > or =2 copies, a high MET gene copy number was observed in 38 patients (54.3%). The characteristics of the 2 groups divided according to MET gene copy number were similar. With a median follow-up duration of 26.4 months (range, 2.6-73.2 months), the estimated 3-year relapse-free survival and overall survival rates were 54.3% and 77.4%, respectively. No significant association was observed between the MET gene copy number and survival in a multivariate analysis. The MET gene copy number investigated in this study was not found to be associated with prognosis in patients with curatively resected gastric cancer.

Diagnostic values of vascular endothelial growth factor and epidermal growth factor receptor for benign and malignant hydrothorax / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hydrothorax, as one of the common complications of malignant tumors, still cannot be sensitively detected in clinical practice, thus requiring a sensitive, specific method for diagnosis. The aim of this study was to analyze the correlation between levels of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in patients with benign and malignant hydrothorax.</p><p><b>METHODS</b>The contents of VEGF in the pleural effusion and serum of the patients with malignant pleural effusion (n = 35) and benign pleural effusion (n = 30) were detected by double antibody sandwich enzyme linked immunosorbent assay. The gene copy number level of EGFR in pleural effusion was detected by fluorescence in situ hybridization (FISH). The points with the highest sensitivity and specificity were selected as the critical values to calculate the diagnostic value of the VEGF in pleural effusion and serum, and EGFR gene copy number in pleural effusion.</p><p><b>RESULTS</b>The contents of VEGF in pleural effusion and serum of patients with malignant hydrothorax were (384.91 ± 120.18), and (129.62 ± 46.35) ng/L, respectively, which were significantly higher than those of the patients with benign hydrothorax (207.97 ± 64.04), (63.49 ± 24.58) ng/L (P < 0.01). The sensitivity and specificity of detecting VEGF in pleural effusion were 80.0% and 96.7% (the boundary value was 297.06 ng/L), respectively for diagnosing benign and malignant hydrothorax. The sensitivity and specificity of serum were 74.3% and 96.7%, respectively (the boundary value was 99.21 ng/L) for diagnosing benign and malignant hydrothorax. The diagnostic efficiencies of EGFR and VEGF in hydrothorax were similar. There was a significant correlation between EGFR and VEGF in hydrothorax (P < 0.01).</p><p><b>CONCLUSIONS</b>VEGF and EGFR play important roles in the formation of pleural effusion. VEGF differed significantly in benign and malignant pleural effusions, which contributed to differential diagnosis results of benign and malignant pleural effusions. It is feasible to detect the gene copy number of the pleural effusion cell mass EGFR by FISH technique. Joint detection can improve the diagnostic sensitivity.</p>

Advance in genetic research on multiple system atrophy / 中华医学遗传学杂志

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder. Widespread presence of glial cytoplasmic inclusions is the neuropathologic hallmark of MSA. The disease has long been considered as a sporadic disorder. However, in recent years, a few familial cases of MSA have been reported, and researches have verified certain genetic variants could increase the risk of MSA. These indicated genetic factors may play an imported role in the pathogenesis of MSA. In this review, the emerging evidence in favor of genetic players in MSA is discussed.

Improving isoprene production by engineered heterologous mevalonate pathway in Escherichia coli / 生物工程学报

Isoprene is an important precursor of synthetic rubber material. In our previous study, metabolic engineered Escherichia coli strain (BW-01) was constructed and used to produce isoprene. Based on the theory of protein budget, using synthetic biology strategies including the increased copy number of genes and rare codons, we regulated the expression of key enzyme to improve isoprene production in Escherichia coli strain. Under shake-flask conditions, isoprene productivity of the engineered strain (BW-07) increased by 73% compared with BW-01, reached 761.1 mg/L. It provides a reference for further studies.

Significance of IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia (B-ALL) in children, and to investigate the association between such abnormalities and prognosis.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) was applied to detect IKZF1 gene copy number abnormalities in 180 children diagnosed with BCR/ABL-negative B-ALL. These children were classified into IKZF1 deletion group and IKZF1 normal group according to the presence or absence of IKZF1 gene deletion. The association between IKZF1 copy number abnormalities and prognosis of children with BCR/ABL-negative B-ALL was analyzed retrospectively.</p><p><b>RESULTS</b>Among 180 children, 27 (15.0%) had IKZF1 deletion; among the 27 children, 4 had complete deletions of 8 exons of IKZF1 gene, 17 had deletion of exon 1, 3 had deletions of exons 4-7, and 3 children had deletions of exons 2-7. Compared with those in the IKZF1 normal group, children in the IKZF1 deletion group had higher white blood cell (WBC) count and percentage of individuals with high risk of minimal residual disease at the first visit. IKZF1 deletions often occurred in BCR/ABL-negative children with no special fusion gene abnormalities. They were frequently accompanied by abnormalities in chromosomes 11, 8, 5, 7, and 21. The analysis with Kaplan-Meier method showed that disease-free survival (DFS) in the IKZF1 deletion group was significantly lower than that in the IKZF1 normal group (0.740 ± 0.096 vs 0.905 ± 0.034; P=0.002). Cox analysis showed that after exclusion of sex, age, initial WBC count, cerebrospinal fluid state at the first visit, prednisone response, and chromosome karyotype, IKZF1 deletion still affected the children's DFS (P<0.05).</p><p><b>CONCLUSIONS</b>Some children with BCR/ABL-negative B-ALL have IKZF1 deletion, and IKZF1 deletion is an independent risk factor for DFS in children with BCR/ABL-negative B-ALL.</p>

Clinical implications of copy number variations in autoimmune disorders

Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as Fcgamma receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and beta-defensin genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication.

Diagnostic value of MYB protein expression in adenoid cystic carcinoma and status of MYB gene copy number / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the diagnostic value of MYB protein expression for adenoid cystic carcinoma and its differential diagnosis from other salivary gland tumors, and to further investigate the status of MYB gene copy number.</p><p><b>METHODS</b>MYB expression was studied by immunohistochemistry in 34 adenoid cystic carcinomas, 55 non-adenoid cystic carcinomas (other salivary gland tumors) including 10 pleomorphic adenomas, 10 basal cell adenomas, 10 epithelial-myoepithelial carcinomas, 9 basal cell adenocarcinomas, 8 mucoepidermoid carcinomas, 4 carcinoma in pleomorphic adenomas, and 4 polymorphous low-grade adenocarcinoma. MYB gene copy number status was detected by FISH in MYB protein-positive cases.</p><p><b>RESULTS</b>82.4% (28/34) of adenoid cystic carcinomas were MYB protein-positive, compared with 9.1% (5/55) of non-adenoid cystic carcinomas, and the difference between the two groups was statistically significant (P < 0.01). 2/18 of adenoid cystic carcinomas had duplication of MYB gene by FISH, and all non-adenoid cystic carcinomas were negative although the difference was not statistically significant (P = 0.435).</p><p><b>CONCLUSIONS</b>MYB protein expression is a useful diagnostic marker for adenoid cystic carcinomas in its separation from other salivary gland tumors. In addition, duplication of MYB gene is no a major mechanism for the MYB protein overexpression.</p>