Clinical phenotype and genetic characteristics of patients with typical 16p11.2 microdeletion syndrome / 中华神经科杂志

Objective:To analyze the clinical phenotype, copy number variation, treatment and follow-up characteristics of children with typical 16p11.2 deletion syndrome.Methods:The clinical data of 10 children with typical 16p11.2 deletion syndrome who were treated in the Department of Neurology, Children′s Hospital of Fudan University from August 2011 to December 2021 were retrospectively collected, and their clinical phenotype, copy number variation, treatment and follow-up were summarized.Results:Among the 10 children, 4 are female and 6 are male, all with epilepsy. Nine patients had epilepsy in infancy, and the age of onset was 6.0 (4.0, 8.5) months. Four cases had focal seizures (1 with fever), 4 had generalized tonic-clonic seizures, and 2 had focal seizures with generalized tonic-clonic seizures. Eight cases had cluster seizures (more than 2 to 10 seizures within 24 hours), and 1 case had 1 status epilepticus. Nine children did not show obvious developmental delay at the onset of epilepsy, and 1 child had developmental delay at the onset of epilepsy at 14 months of age. One child had parallel toes at left foot, and 1 had macrocephaly and low limb muscle tone. Genetic testing found that 10 children carried typical 16p11.2 heterozygous deletion, the starting position of the deletion fragment was Chr16:29478119-29675016, the ending position was Chr16:30125670-30206112, and the deletion length was 525-712 kb, all of which were considered pathogenic variants. In the antiepileptic drug treatment, 4 children were treated with oxcarbazepine, 2 with sodium valproate, 2 was switched to oxcarbazepine after levetiracetam was ineffective, 1 with levetiracetam combined with sodium valproate, and 1 with levetiracetam in combination with sodium valproate and ketogenic diet, and all 10 children had no seizures. One patient developed episodic exercise-induced dyskinesia at school age, and the seizures decreased after treatment with oxcarbazepine. Follow-up of 10 children found that 9 children had different degrees of developmental delay (language was significantly affected), 3 cases were combined with autism-like manifestations, and 1 case had poor comprehension, learning difficulties, and repeated grades after entering regular primary schools.Conclusion:The typical 16p11.2 microdeletion syndrome has the deletion of gene fragments in the proximal region of 16p11.2, characterized by drug-responsive cluster seizures with onset in infancy, which may be accompanied by language delay, autism spectrum disorder and nonspecific malformations.

Etiological identification and phylogenetic analysis of a clustered epidemic caused by norovirus on a patrol boat / 上海预防医学

ObjectiveTo determine the pathogen and phylogenetic characteristics of an uncommon outbreak of recombinant norovirus infection in Daishan County in February 2022. MethodsFluorescence quantitative PCR was used to detect the norovirus in the eight anal swabs collected in the outbreak. In the positive samples， reverse transcription PCR were used to amplify the norovirus. Norovirus sequences were characterized by MEGA7 and Simplot. ResultsNorovirus GⅠ was identified in all eight anal samples. It was further determined to be recombinant norovirus GⅠ.6 ［P11］， with the recombination site at the ORF1-ORF2 junction. The sequence had the highest nucleotide identity （98.75%） to a GⅠ.6［P11］ strain collected in 2018 （GenBank accession number MT357995）. ConclusionAccording to the etiological identification and phylogenetic analysis， this outbreak is confirmed to be caused by the uncommon recombinant norovirus GⅠ.6 ［P11］ in China.

Clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.@*METHODS@#The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed.@*RESULTS@#The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children.@*CONCLUSIONS@#16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.

Effect of preconditioning the fractured coronal fragments with remineralizing agents on fracture resistance of re-attached teeth

Background: Fragment re-attachment has been considered as one of the treatment modalities for the management of fractured anterior teeth. Hydration of fractured fragments aids in inhibiting the loss of ions and maintains vitality and esthetics. Aim: The study aimed to evaluate the effect of preconditioning the fractured fragments with remineralizing agents on fracture resistance of re-attached teeth. Settings and Design: This was an in vitro study. Materials and Methods: Sixty freshly extracted noncarious human permanent maxillary central and lateral incisors were randomly allocated into three Groups of 20 each: Group 1: 2% sodium fluoride (2%NaF), Group 2: casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), and Group 3: self-assembling peptide P11-4 (SAP). These were further divided into two subgroups of 10 teeth each, based on contact time with remineralizing agents, i.e., 30 min and 2 h. Fractured fragments were treated with remineralizing agents for a specified contact time and then re-attached with flowable composite resin. Force required to fracture the re-attached tooth was recorded in Newtons using universal testing machine. Statistical Analysis: Unpaired t-test, one-way analysis of variance test, and post hoc Tukey test were used for the statistical analysis. Results: A higher fracture resistance was noticed in fragments treated with 2% NaF (30 min- 215.6 N, 2 h- 188.5 N) compared to CPP-ACP (30 min- 141.3 N, 2 h- 111.1 N) and SAP (30 min- 134.8 N, 2 h- 149.5 N). At 30 min interval, it was found to be more in 2% NaF and CPP-ACP groups compared to 2 h. However, it increased with time in the SAP group. A statistically significant difference was found between the groups at both time intervals (P = 0.007 and 0.017). Conclusion: Preconditioning of fractured coronal fragments with 2% NaF showed higher fracture resistance compared to CPP-ACP and self-assembling peptide P11-4. Samples treated with SAP P11-4 exhibited good fracture resistance at 2 h contact time.

Prenatal diagnosis and neonatal phenotype of a de novo microdeletion of 17p11.2p12 associated with Smith–Magenis syndrome and external genital defects

Smith–Magenis syndrome (SMS, OMIM: 182290) is a multiple congenital anomalies and intellectual disability syndrome due to a 3.45 Mb microdeletion involving 17p11.2 and is estimated to occur about one in 25,000 births. Up to now, the ultrasound findings of the foetus with SMS and their external genital defects in patients are rarely reported. This case indicates that foetus with SMS may present polyhydramnios and ventriculomegaly in the second trimester. The newborn male patient had an abnormal phenotype in which he has micropenis and his anus is close to the perineal body. The identification of this case may further expand the phenotypic spectrum of this genetic disorder.

Comparison between Fluorescence in-situ Hybridization (FISH), Reverse Transcriptase PCR (RT-PCR) and fragment analysis, for detection of t (X; 18) (p11; q11) translocation in synovial sarcomas

Background: Synovial sarcoma (SS) is an aggressive, but a relatively chemosensitive soft tissue sarcoma, characterized by a specific, t (X;18)(p11;q11) translocation, leading to formation of SS18–SSX chimeric transcript. This translocation can be detected by various techniques, such as fluorescence in-situ hybridization (FISH), reverse transcriptase PCR (RT-PCR) and fragment analysis. Objectives: To compare the results of detection of t (X;18)(p11;q11) translocation, across three different platforms, in order to determine the most optimal and sensitive technique. Methods: Formalin-fixed paraffin embedded (FFPE) tissue sections of 45 soft tissue sarcomas were analyzed, including 16 cases of SS confirmed by histopathology, immunohistochemistry and molecular technique (s)(Group 1); 13 cases, wherein SS was one of the differential diagnosis, preceding molecular testing (Group 2) and 16 cases of various other sarcomas (Group 3). Various immunohistochemical (IHC) markers studied, including INI1/SMARCB1. All cases were tested for t (X;18) translocation, by fragment Analysis, FISH and RT-PCR. Results: There were 23 cases of SS, including 16 of group 1 and 7 of group 2. By fragment analysis, t (X;18)(p11;q11) translocation was detected in 22/23 cases (95.6%). By FISH, SS18 gene rearrangement was detected in 18/22 cases (78.2%), whereas by RT-PCR, SS18-SSX transcripts were detected in 15/23 cases (65.2%). Immunohistochemically, a unique “weak to absent”/reduced INI1 immunostaining pattern was exclusively observed in 12/13 cases of SS (92.3%). Fragment analysis and FISH were relatively more sensitive techniques. Unique “weak to absent”INI1 immunoexpression significantly correlated with positive t (X;18) translocation results (P = 0.0001). Conclusion: The present study constitutes first such study from our subcontinent. Fragment analysis is a promising technique for detection of t (X;18)(p11;q11) translocation. FISH and INI1 immunostaining pattern were also relatively more sensitive, over RT-PCR.

Down-regulation effects of IFN-alpha on p11, 5-htr1b and 5-HTR4 protein levels were affected by NH4CL or MG132 treatment in SH-sy5y cells

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed aftertreatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterallyovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX?OA control, OVX?OA ? diclofenac (5 mg/kg) (positive control), OVX?OA ? LP leaf extract (150 and300 mg/kg) and healthy sham control. After 8 weeks’ treatment, their conditions were evaluated via serum biomarkers,knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilageerosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenacand the non-treated OA. The cartilage catabolic markers’ (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa,CASP3 and HIF-2a) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased byLP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilageprotective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondralbone restoration. The cartilage ERa over-expression showed a strong positive correlation with MMP-13, COL10a1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.

Reflection of a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotyping analysis / 中华医学遗传学杂志

Objective@#To emphasize the clinical significance of copy number variations (CNVs) detection by describing a case misdiagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis.@*Methods@#A girl with obesity and short stature was diagnosed as trisomy 21 syndrome by G-banded chromosomal karyotype analysis. Considering the discrepancy of her karyotype with her phenotype, genomic CNVs was detected by next-generation sequencing and the result was verified by quantitative PCR (qPCR).@*Results@#A microduplication of 16p11.2: 29 642 339-29 775 631 (133.292 kb) was detected. qPCR assay for QPRT and SPN located in the duplicated region confirmed the finding of CNVs assay. Meanwhile, her parents did not present similar duplication in 16p11.2.@*Conclusion@#The 16p11.2 microduplication was a novel genomic structural variation in the girl, though it may not be associated with her clinical manifestations. Chromosomal microarray or next-generation sequencing-based CNVs detection can accurately determine the origin of small supernumerary marker chromosome and reduce the chance of misdiagnosis.

Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells / 中华血液学杂志

Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1. Results: BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression. Conclusion: Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.

Expression and clinical significance of lncRNA RP11-259P1.1 in small cell lung cancer tissues / 中国肿瘤生物治疗杂志

@#Objective: To explore the expression of long non-coding RNA RP11-259P1.1 (lncRNA RP11-259P1.1) in small cell lung cancer (SCLC) tissues and to analyze the relationship between lncRNARP11-259P1.1 expression and SCLC clinicopathological characteristics, as well as to investigate its effect in chemoresistance. Methods: Tissue samples, including 158 cases of tumor tissues from SCLC patients, who underwent bronchoscopic biopsy, puncture biopsy and surgical resection, 48 cases of para-cancerous tissues and 40 cases of normal lung tissues, collected from January 2012 to December 2016 in the Sixth People’s Hospital of Chengdu and General Hospital of Chengdu Military Region，were used in this study. The expression of lncRNARP11-259P1.1 was detected by Real-time fluorescence quantitative PCR (qPCR). χ2 test was used to analyze the relationship between the expression of lncRNA RP11-259P1.1 and the clinicopathological characteristics as well as chemotherapeutic resistance in SCLC patients. Relationship between lncRNA RP11259P1.1 expression and prognosis of SCLC patients was analyzed by univariate and multivariate Cox regression analysis. Results: The expression of lncRNA RP11-259P1.1 in SCLC tissues was significantly higher than that in para-cancerous tissues and normal lung tissues (all P < 0.01). The expression of lncRNA RP11-259P1.1 in cancer tissues of chemosensitive group was significantly lower than that of chemoresistant group (P<0.05). The expression of lncRNA RP11-259P 1.1 was not correlated with gender and age, but significantly correlated with tumor stage, metastasis and chemosensitivity (all P<0.05). PFS and OS in patients with high lncRNA RP11-259P 1.1 expression were significantly shorter than those in patients with low expression ([12.25±1.83] vs [22.29±1.58] months, [23.55±1.35] vs [31.75±2.43] months, all P<0.01). The expression of lncRNA RP11-259P 1.1, tumor stage and distant metastasis were the independent prognostic factors in SCLC patients (all P<0.05). Conclusion: The high expression of lncRNA RP11-259P1.1 in SCLC tissues is associated with chemosensitivity and prognosis of SCLC patients, and may be a potential biomarker for prognosis evaluation in SCLC patients.

Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells / 中华血液学杂志

Objective@#To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro.@*Methods@#Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1.@*Results@#BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression.@*Conclusion@#Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.

Microdeleción 16p11. 2: primeros casos reportados en Argentina / 16p11. 2 Microdeletion: first report in Argentina

La microdeleción 16p11.2 se relaciona, habitualmente, con discapacidad intelectual y trastornos del espectro autista. El rango fenotípico incluye un espectro que se extiende desde discapacidad intelectual con o sin autismo, alteraciones del aprendizaje y del lenguaje hasta fenotipos normales. El diagnóstico de la microdeleción se realiza mediante estudios genómicos capaces de identificar variación en número de copias, como la hibridación genómica comparativa en microarreglos, conocida como arrayCGH. Sin embargo, la predicción del fenotipo de un individuo basada únicamente en la localización de dicha deleción sigue siendo un desafío, ya que la existencia de un gran número de variantes en el genoma dificulta la interpretación de posibles efectos funcionales de los genes que contribuyen a dicha región. Se describen dos casos clínicos de pacientes con microdeleción heterocigota en 16p11.2 y se destacan los hallazgos fenotípicos y conductuales que dificultaron la estrategia diagnóstica. También se discuten las implicancias del diagnóstico para el asesoramiento genético familiar.

The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder. This microdeletion is associated with variable clinical outcome, the phenotypical spectrum ranges from intellectual disability and/or multiple congenital anomalies, autism, learning and speech problems, to a normal phenotype. Genomic testing that determines copy number of sequences, such as chromosomal microarray, is used to identify this microdeletion. However, the prediction of the individual phenotype of a patient based only on the location of such deletion remains a challenge, regarding the existence of many genomic variants that might hinder the interpretation of possible functional effects between most of the contributing genes to that region. We describe the clinical findings in two subjects with heterozygous microdeletions at 16p11.2, highlighting the phenotypic and behavioural findings that conditioned the diagnostic strategy. We also discuss the implications of diagnosis, in practical counselling situations.

Neu-P11 reduces IOP through inhibiting oxidative stress level of acute high IOP rats / 中国药理学通报

Aim To explore the effect of Neu-P11,a novel melatonin agonist with similar function of melatonin,on IOP of acute high IOP animals and the related mechanism.Methods The experiment used the Trendelenburg position(head low feet high position of 80°)to establish acute high IOP model.Rats were placed in the Trendelenburg position and used Tonopen XL contact tonometer to measure IOP(every 5 minutes measured once IOP,and the maximum value in 20 minutes)in 8 :00～9 :00 am.And then,thirty Sprague-Dawley rats(8 week-old)were divided into five groups: normal IOP+normal saline,high IOP+normal saline,high IOP+10 mg·kg-1 Mel,high IOP+20 mg·kg-1 Neu-P11,high IOP+50 mg·kg-1 Neu-P11.Put in a flat to rest 2 h,animals were placed in Trendelenburg position again and then,IOP was measured every hour in the flat by 6 hours.After excessive sodium pentobarbital administration continuous for 1 week,the serum was collected and stored for subsequent detection at the end of the experiment.The level of MDA,SOD and GSH-Px enzyme activity of the rat serum was tested by kit accordingly.HE staining method was used to identify the SD rat retinal morphological changes.Results Trendelenburg position could induce IOP of model group rats,which was increased by 202.9％(P<0.01)and the content of MDA,reduced the activity of SOD and GSH-Px enzyme,retinal thickening was observed and its level was not clear.Neu-P11/Mel could significantly improve oxidative stress level and retinal edema in rats.Conclusion Neu-P11 could reduce IOP of the acute high IOP animals,which might be involved in the lower level of oxidative stress in the body.

Effect of Neu-P11 on retinal GFAP protein expression and IOP of acute high IOP rats / 眼科新进展

Objective To explore the effects of the new melatonin nonselective agonists Neu-P11 on intraocular pressure (IOP) and glial fibrillary acid protein (GFAP) expression in the retina of acute high IOP rat.Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups (6 cases in each group):Normal IOP with local treatment (NIL) group,high IOP with local treatment (HIL) group,HILwith melatonin treatment (HIL-M) group,HIL with Neu-P11 treatment (HIL-N) group.10 μL normal saline was instilled in NIL group and HIL group,while 10 μL 100 μmol · L-1 Mel/Neu-P11 treated in HIL-M group and HIL-N group.After 2 hours of rest,rats were placed in the Trendelenburg position duration 45 minutes.And then,IOP was measured every hour for 6 hours,and repeated it for a week.The excessive sodium pentobarbital was injected to SD rats at the end of the experiment.The rat eyeballs were took out to perform HE and immunohistochemical staining to detect retina GFAP protein expression.Results After a week,IOP in HIL group was (41.26 ± 1.73) mmHg (1 kPa =7.5 mmHg),NIL group was (13.61 ± 0.55) mmHg,which mean the Trendelenburg could induce high IOP in SD rats.Compared with the NIL group,the retinal becoming thick,the level of organization was not clear and the expression of GFAP protein was quite high in HIL group.At the same time,the GFAP protein expression and IOP were significantly weakened in HIL-M group and HIL-N group compared with HIL group.Conclusion Neu-P1 1 can reduce IOP,inhibit the activation of gliocyte,and decrease the expression of GFAP to protect the retina.

Duplication 17p11.2 (Potocki-Lupski Syndrome) in a child with developmental delay

Potocki-Lupski syndrome (PTLS), also known as duplication 17p11.2 syndrome, trisomy 17p11.2 or dup(17)(p11.2p11.2) syndrome, is a developmental disorder and a rare contiguous gene syndrome affecting 1 in 20,000 live births. Among the key features of such patients are autism spectrum disorder, learning disabilities, developmental delay, attention-deficit disorder, infantile hypotonia and cardiovascular abnormalities. Previous studies using microarray identified variations in the size and extent of the duplicated region of chromosome 17p11.2. However, there are a few genes which are considered as candidates for PTLS which include RAI1, SREBF1, DRG2, LLGL1, SHMT1 and ZFP179. In this report, we investigated a case of a 3-year-old girl who has developmental delay. Her chromosome analysis showed a normal karyotype (46,XX). Analysis using array CGH (4X44 K, Agilent USA) identified an ~4.2 Mb de novo duplication in chromosome 17p11.2. The result was confirmed by fluorescence in situ hybridization (FISH) using probes in the critical PTLS region. This report demonstrates the importance of microarray and FISH in the diagnosis of PTLS.

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

ABSTRACT Background: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24 months old), based on the presence of hemophagocytosis by blast cells at diagnosis. Methods: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Results: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive. Conclusions: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis.

Drosophila Homolog of Human KIF22 at the Autism-Linked 16p11.2 Loci Influences Synaptic Connectivity at Larval Neuromuscular Junctions

Copy number variations at multiple chromosomal loci, including 16p11.2, have recently been implicated in the pathogenesis of autism spectrum disorder (ASD), a neurodevelopmental disease that affects 1~3% of children worldwide. The aim of this study was to investigate the roles of human genes at the 16p11.2 loci in synaptic development using Drosophila larval neuromuscular junctions (NMJ), a well-established model synapse with stereotypic innervation patterns. We conducted a preliminary genetic screen based on RNA interference in combination with the GAL4-UAS system, followed by mutational analyses. Our result indicated that disruption of klp68D, a gene closely related to human KIF22, caused ectopic innervations of axon branches forming type III boutons in muscle 13, along with less frequent re-routing of other axon branches. In addition, mutations in klp64D, of which gene product forms Kinesin-2 complex with KLP68D, led to similar targeting errors of type III axons. Mutant phenotypes were at least partially reproduced by knockdown of each gene via RNA interference. Taken together, our data suggest the roles of Kinesin-2 proteins, including KLP68D and KLP64D, in ensuring proper synaptic wiring.

Prenatal diagnosis of an unbalanced translocation between chromosome Y and chromosome 15 in a female fetus

We report the prenatal diagnosis of an unbalanced translocation between chromosome Y and chromosome 15 in a female fetus. Cytogenetic analysis of parental chromosomes revealed that the mother had a normal 46,XX karyotype, whereas the father exhibited a 46,XY,der(15)t(Y;15) karyotype. We performed cytogenetic analysis of the father's family as a result of the father and confirmed the same karyotype in his mother and brother. Fluorescence in situ hybridization and quantitative fluorescent-polymerase chain reaction analysis identified the breakpoint and demonstrated the absence of the SRY gene in female members. Thus, the proband inherited this translocation from the father and grandmother. This makes the prediction of the fetal phenotype possible through assessing the grandmother. Therefore, we suggest that conventional cytogenetic and molecular cytogenetic methods, in combination with family history, provide informative results for prenatal diagnosis and prenatal genetic counseling.

Role of p11 (S100A10) in Depression and Antidepressant Effects

p11 protein (S100A10) is downregulated in depressive-like states of human and rodent. Antidepressant drug treatment increases p11 levels in rodent models. We reviewed studies demonstrating that p11 levels are regulated in depression and by antidepressant treatment and that p11 upregulation exerts antidepressant effects. Current studies on p11 underscore the importance of p11 as a potential antidepressant target.

Effect of melatonin receptor agonist Neu-P11 on phosphorylation of protein kinase B in mouse 3T3-L1 adipocytes / 第二军医大学学报

Objective: The objective of present study was to examine the changes of melatonin receptor agonist Neu-P11 on expression of PKB and P-PKB in 3T3-L1 adipocytes and to research the variation mechanisms.Methods: 3T3-L1 pre-adipocytes were cultivated and differentiated in adipogenic cocktail by IBMX, DEX and insulin; Confirm the establishment of insulin resistance model. The changes of PKB and P-PKB protein expressions before and after drug action were detected by Western blot; Results: Expression of PKB and P-PKB reduced significantly by comparison with IS (P < 0.05). Melatonin and Neu-P11 can increase obviously the expression of PKB and P-PKB (P < 0.05). But Luzindole can block the effect of melatoninl, Neu-P11 increasing PKB (P < 0.05), will also be able to block that the melatonin increase P- PKB (P < 0.05), but it can"t block that Neu-P11 increases P - PKB .