Transient neonatal diabetes mellitus with subtype ZFP57 genetic defect in 6q24

Neonatal diabetes (NDM) is a rare form of diabetes that manifests in the first few months of an infant's life. The condition affects approximately one in 300,000 to 400,000 newborns and is characterized by elevated blood glucose levels. Transient and permanent NDM are the two types of this disease. In most cases of transient neonatal diabetes mellitus (TNDM), the genetic cause has been attributed to the overexpression of chromosome 6q24. Regardless of its underlying cause, the primary treatment for neonatal diabetes is insulin therapy.

Síndrome de Miller-Dieker: reporte de dos casos / Miller-Dieker Syndrome: Two Cases Report

Resumen Introducción: El síndrome de Miller-Dieker cuenta con un patrón de herencia autosómico dominante y pertenece al grupo de trastornos de la migración neuronal. Se caracteriza por la presencia de lisencefalia de tipo 1, retraso global del desarrollo, microcefalia, epilepsia y dismorfismos faciales dados por mutaciones en el cromosoma 17p13. El síndrome de Miller-Dieker es una enfermedad extremadamente rara con prevalencia de 1 caso por cada 100,000 recién nacidos vivos. Presentación de casos: Nosotros presentamos dos casos de síndrome de Miller-Dieker en los que datos de la exploración física y del interrogatorio fueron pistas que permitieron una fuerte sospecha diagnóstica y que a su vez el diagnóstico definitivo mediante FISH permitió brindar un adecuado manejo con la finalidad de mejorar el pronóstico a largo plazo. Conclusión: Se debe tener una alta sospecha diagnóstica mediante la exploración física dirigida a identificar alteraciones en pacientes con epilepsia de difícil control, ya que permite guiar el diagnóstico etiológico y con ello brindar un adecuado tratamiento.

Abstract Introduction: Miller-Dieker syndrome has an autosomal dominant pattern of inheritance and belongs to the group of neuronal migration disorders. It is characterized by the presence of type 1 lissencephaly, global development delay, microcephaly, epilepsy and facial dysmorphisms caused by mutations in chromosome 17p13. Miller-Dieker syndrome is an extremely rare disease with a prevalence of 1 case per 100,000 live births. Case presentation: We present two cases of Miller-Dieker syndrome in which data from the physical examination and questioning were clues that allowed a strong diagnostic suspicion and that, in turn, the definitive diagnosis by means of FISH allowed us to provide adequate management in order to improve the long-term prognosis. Conclusion: A high diagnostic suspicion must be achieved through physical examination aimed at identifying alterations in patients with difficult-to-control epilepsy, since it allows guiding the etiological diagnosis and thereby providing adequate treatment.

High prevalence of D/G group acrocentric RPL chromosome polymorphisms in 1400 recurrent pregnancy losses patients, an evaluation of genetic factor and reassessing CPMs in 21st century as normal variants?

Background: The current burden for recurrent pregnancy losses in India is quite high and is around 7.4% and majority of them with no definitive cause for pregnancy loss even after complete RPL workup. The objective of the study was to investigate the prevalence and possible association of chromosome polymorphisms with recurrent pregnancy loss patients.Methods: A single centre case-control retrospective study on RPL patients undergoing conventional cytogenetics culture techniques to rule out chromosome abnormalities.Results: The prevalence of chromosome polymorphism in the study was 33.7% (471/1400) high in comparison to previous studies. The acro ps+/- polymorphisms involving D/G group of chromosomes was significantly higher in the study group observed in 23.5% (330/1400) patients and 15.8% (58/366) in the control group p <0.005. The prevalence of 22ps+ subtype polymorphism was significantly higher in the patient groups with the odd ratio OR (95% CI)- 2.35 (1.245-4.434).Conclusions: This study substantiates the very high prevalence of CPMs and therefore should be interpreted cautiously till further strong evidence are available, until then patient should be counselled on case-to case basis. In future CPMs may play a crucial role in prognosis and management in unexplained RPL group with no other definitive cause identified after RPL workup as per recommendations from international and national guidelines.

Aortic stenosis of fetus caused by chimeric Y-chromosome isobaric double-adherent granules:A case report and literature review / 吉林大学学报(医学版)

Objective:To confirm the potential etiological factors of congenital aortic stenosis(AS)by genetic analysis on prenatal diagnostic results of the fetus with AS.Methods:Amniocentesis for chromosomal G-band karyotyping combinated with single nucleotide polymorphism array(SNP-array)analysis was conducted on the amniotic fluid collected from a 25-week pregnant woman diagnosed as"fetus AS";chromosome karyotyping was also performed on the peripheral blood of the fetal parents.Results:The fetal karyotype analysis showed a chimeric Y-chromosome isobaric double-adherent granules.The SNP-array analysis results revealed a 11.2 Mb duplication in the Yp11.31q11.21 region and a 14.8 Mb deletion in the Yq11.21q11.23 region.Both the parents presented a normal karyotype,suggesting it was a newfound mutation.After extensive genetic counseling,the pregnant woman and her family chose to terminate the pregnancy locally.Conclusion:The chromosomal karyotype of the chimeric Y-chromosome isobaric double-adherent granules may be a contributing factor to the AS phenotype in the male fetus.The combined use of chromosomal karyotyping and SNP-array analysis on the amniotic cells is instrumental in the early diagnosis of the disease.

The relationship between serum CXCL1 and PTEN mRNA levels and disease severity and prognosis in patients with acute cerebral infarction / 国际检验医学杂志

Objective To investigate the relationship between the levels of serum CXC chemokine ligand 1(CXCL1)and phosphatase and tensin homology deleted on chromosome ten(PTEN)mRNA in patients with acute cerebral infarction and the severity and prognosis of the disease.Methods A total of 102 patients with acute cerebral infarction admitted to the hospital from March 2022 to March 2023 were enrolled in the study as the experimental group,and 85 healthy people who underwent physical examination in the hospital during the same period were enrolled as the control group.Serum samples of fasting venous blood were collected from people enrolled in the study.The serum CXCL1 level was detected by using enzyme-linked immunosorbent as-say.Real-time fluorescence quantitative PCR(qPCR)was used to detect the relative expression level of serum PTEN mRNA(hereinafter referred to as the level).According to the National Institutes of Health Stroke Scale(NIHSS)score,the patients in the experimental group were divided into three groups with different de-grees of neurological impairment(severe group,moderate group and mild group),and the serum CXCL1 and PTEN mRNA levels of the three groups were compared.According to the cerebral infarction volume evaluated by computed tomography(CT)or magnetic resonance imaging(MRI),the patients in the experimental group were divided into small infarction group,medium infarction group and large infarction group,and the serum CXCL1 and PTEN mRNA levels of the three groups were compared.According to the modified Rankin scale(mRS),the patients in the experimental group were divided into the good prognosis group and the poor prog-nosis group,and the serum CXCL1 and PTEN mRNA levels were compared between the two groups.Pearson correlation was used to analyze the correlation between serum CXCL1 and PTEN mRNA levels in patients with acute cerebral infarction.Multivariate Logistic regression analysis was used to analyze the factors affect-ing the prognosis of patients with acute cerebral infarction.Results The proportion of patients with a history of diabetes and hypertension and serum CXCL1 and PTEN mRNA levels in the experimental group were high-er than those in the control group,and the differences were statistically significant(P＜0.05).With the in-crease of the degree of neurological impairment,the serum CXCL1 level and PTEN mRNA level increased,and there were significant differences among the severe group,moderate group,and mild group(P＜0.05).With the increase of infarction size,the serum levels of CXCL1 and PTEN mRNA increased,and there were signifi-cant differences among small infarction group,medium infarction group,and large infarction group(P＜0.05).Compared with the good prognosis group,the poor prognosis group had significantly higher proportions of patients with a history of diabetes,a history of hypertension,and serum CXCL1 and PTEN mRNA levels(P＜0.05).There was a positive correlation between serum CXCL1 level and PTEN mRNA level in patients with acute cerebral infarction(r=0.479,P＜0.001).The levels of serum CXCL1 and PTEN mRNA,history of diabetes and hypertension were all influencing factors for the prognosis of patients with acute cerebral in-farction(P＜0.05).Conclusion The levels of serum CXCL1 and PTEN mRNA in patients with acute cere-bral infarction increase,which can be used to evaluate the disease severity and prognosis of patients.

Regulatory effect of C12ORF66 on viability of MYCN amplified high-risk neuroblastoma cells / 基础医学与临床

Objective To explore the effect of open reading frame 66(C12ORF66)located at chromosome 12 on the viability of MYCN amplified NB cell lines.Methods DDatasets GSE16476 and GSE49710 in R2 database were analyzed for expression level of C12ORF66 in MYCN amplified and MYCN non-amplified NB cells and its potential correlation with the prognosis of pediatric patients.C12ORF66 mRNA expression level in normal tissue immortalized cell lines,MYCN amplified and MYCN non-amplified cell lines were detected by RT-qRCR.Transient or stable knockdown of C12ORF66 cell lines were constructed to compare the difference in real time cellular analysis(RTCA),colony formation,Ki67 positive cells between the control group and the C12ORF66 knockdown group.Results By analyzing R2 datasets,C12ORF66 level in MYCN amplified samples was significantly higher than that in MYCN non-amplified samples,and the expression of C12ORF66 was negatively correlated with the prognosis of pediatric patients(P＜0.05).C12ORF66 highly expressed in MYCN-amplified BE(2)-C and SK-N-BE(2)cell lines than in MYCN non-amplified CHLA-255 and SH-SY5Y cell lines(P＜0.001).Transient or stable knockdown of C12ORF66 resulted in significant slow down of proliferation of MYCN amplified NB cells(P＜0.001),the colony formation ability was significantly reduced(P＜0.001),and the proportion of Ki67 positive cells was significantly decreased(P＜0.05).Conclusions C12ORF66 was highly expressed in MYCN amplified clinical NB samples and cell lines which is believed to be correlated with poor prognosis of pediatric patients.C12ORF66 knockdown signifi-cantly inhibits cell viability of NB cells.

Analysis of abnormal karyotype and clinical manifestations of 4 157 infertility patients in Southern Sichuan Province / 临床检验杂志

Objective To investigate the distribution of abnormal karyotypes and their associations with clinical manifestations of the infertile patients in southern Sichuan Province.Methods A total of 4 157 infertile patients who attended the Reproductive Medicine Center of our hospital from July 2018 to June 2021 were included.The chromosome karyotype in peripheral blood was detected by G-banding,and their semen analysis results,uterine development and other clinical data were collected.Results Among the 4 157 patients,chromosomal polymorphisms were found in 239 cases(5.75％),and abnormal karyotypes wee found 137 cases(3.30％).The abnormal karyotypes included 57 cases(41.61％)of sex chromosome aneuploidy,6 cases(4.38％)of Robertsonian transloca-tions,32 cases(23.36％)of balanced translocations,21 cases(15.33％)of chromosomal inversions,9 cases(6.57％)of mosai-cism,8 cases(5.84％)of marker chromosomes,3 cases(2.19％)of sex reversal and 1 case(0.73％)of sex chromosome deletion.In male patients with abnormal karyotypes,91.58％showed abnormal semen parameters,while in those with polymorphic karyotypes,55％had abnormal semen parameters.The patients with Turner syndrome had significantly smaller uterine dimensions(longitudinal,transverse,and anteroposterior)compared to the normal control group(P＜0.01).Conclusion Chromosomal abnormalities should be the important cause of infertility.Conducting karyotype analysis combining with clinical manifestations is crucial examination for the di-agnosis and reproductive guidance of infertile patients.

Erythropoietin-overexpressed umbilical cord mesenchymal stem cells inhibit neuroapoptosis in ischemic-hypoxic SH-SY5Y and its mechanism / 中国组织工程研究

BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.

Analysis of intercomparison results of national biological dose estimation capability in 2022 / 中华放射医学与防护杂志

Objective:To improve the ability of radiation health technical institutions for biological dose estimation.Methods:A total of 144 institutions nationwide, including the CDC, prevention and treatment center for occupational disease, colleges and universities, scientific research institutes, nuclear industry systems, and medical and physical examination institutions, were organized to carry out the intercomparison of national biological dose estimation capabilities in 2022. The institutions participating in the comparison were divided into two types of A and B, through the identification of chromosome aberrations, to estimate the irradiation dose (A) or chromosome aberration rate (B). The results were summarized and compared, and the main problems were analyzed and discussed.Results:There were 60 institutions in type A, 52 qualified institutions (including 12 excellent institutions) and 8 unqualified institutions, with a pass rate of 86.7% (20.0% excellent) and a failure rate of 13.3%. There were 84 institutions participating in the biological dose estimation comparison of type B, with 48 qualified institutions, and 36 unqualified institutions, the qualified rate was 57.1%, and the unqualified rate was 42.9%.Conclusions:Most of the institutions participating in type A comparison have the ability to estimate biological dose, and more than half of the institutions participating in type B comparison have the ability to analyze chromosome aberration. The overall ability of institutions participating in type A comparison is higher than in type B.

Serum levels of SOX6 and PTEN and their clinical significance in patients with acute myocardial infarction / 中华老年心脑血管病杂志

Objective To investigate the expression and clinical significance of SRY-box transcrip-tion factor 6(SOX6)and protein tyrosine phosphatase gene(PTEN)in patients with acute myo-cardial infarction(AMI).Methods A total of 100 AMI patients admitted to Zibo First Hospital and Zibo Central Hospital from January 2021 to March 2022 were enrolled as the study group,and according to the occurrence of major adverse cardiovascular events(MACE),they were grouped into MACE subgroup(52 cases)and non-MACE subgroup(48 cases).Another 110 volunteers who taking physical examination in above 2 hospitals during the same period were subjected as the control group.The levels of PTEN and SOX6 in the serum were detected,and Pearson correla-tion analysis was performed to investigate the correlation of serum PTEN and SOX6 levels with clinical indicators.ROC curve was drawn to assess the diagnostic value of PTEN and SOX6 levels for diagnosis and prognosis of AMI.Results The study group had significantly decreased serum mRNA level of SOX6(0.69±0.14 vs 1.03±0.16,P＜0.01)and increased serum mRNA level of PTEN(1.56±0.15 vs 1.05±0.08,P＜0.01)than the control group.Similar results were seen in the MACE subgroup than the non-MACE subgroup(SOX6:0.61±0.15 vs 0.78±0.13,P＜0.01;PTEN:1.74±0.18 vs 1.37±0.12,P＜0.01).Pearson correlation analysis showed that the serum level of PTEN was positively,and that of SOX6 was negatively correlated with cTnI,CK-MB and Gensini score(P＜0.01).ROC curve analysis indicated that the AUC value of combined serum SOX6 and PTEN levels for diagnosis of AMI was 0.932(95％CI:0.889-0.962),and that for pre-dicting MACE was 0.933(95％CI:0.866-0.974).Conclusion The serum level of SOX6 is down-regulated,and that of PTEN was up-regulated in AMI patients.Their combined detection is help-ful for diagnosis of AMI and prediction of MACE.

Establishment and validation of a dose-response curve for semi-automatic analysis of dicentric chromosomes / 中国职业医学

ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D2 (R2= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.

Sub-chronic aluminum exposure induces cognitive impairment through ALKBH5/PTEN/AKT signaling pathway in rats / 中国职业医学

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten/phosphoinositol 3 kinase/protein kinase B axis on apoptosis of renal tissue cells in rats with diabetic kidney disease / 中国糖尿病杂志

Objective To investigate the effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten(PTEN)/phosphoinositide 3 kinase(PI3K)/protein kinase B(AKT)pathway on renal tissuecell apoptosis in diabetic kidney disease(DKD)rats.Methods The DKD rat model was constructed by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).72 rats were divided into normal control group(NC),DKD model group(DKD),miR-130a agonist negative control group(NC agomir),and miR-130a agonist group(miR-130a agomir),miR-130a agomir+ PTEN overexpression negative control group(miR-130a agomir+pcDNA),and miR-130a agomir+ PCDNA-PTEN overexpression group(miR-130a Agomir + PCDNA-PTEN),with12 rats in each group.Urinary microalbumin kit was used to detect 24 h urine albumin(UAlb).Fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by automatic biochemical analyzer.Pathological changes of renal tissue were detected by HE staining.The levels of serum IL-6 and TNF-α were detected by ELISA.The apoptosis of renal tissue was detected by TUNEL staining.The expression of miR-130a was detected by qRT-PCR,and the expression of B-cell lymphoma-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2)and PTEN/PI3K/AKT pathway were detected by Western blot.Dual luciferase reporter gene experiment was used to verify the targeting relationship between miR-130a and PTEN.Results Compared with DKD and NC agomir groups,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression in miR-130a agomir group were decreased(P＜0.05).The expressions of miR-130a,Bcl-2,p-Akt/AKT protein were increased(P＜0.05).Compared with miR-130a agomir group,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression were increased in miR-130a agomir+pcDNA-PTEN group(P＜0.05).The expression of Bcl-2,p-Akt/AKT protein decreased(P＜0.05).Conclusion Overexpression of miR-130a may inhibit renal cell apoptosis in DKD rats by down-regulating PTEN to activate PI3K/AKT pathway.

Prevalence of karyotype alterations in couples with recurrent pregnancy loss in a tertiary center in Brazil

Abstract Objective To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities. Methods We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding. Results Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations. Conclusion The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

DELEÇÃO 14q24.1: características fenotípicas e resposta ao uso hormônio do crescimento recombinante humano / 14q24.1 DELETION: phenotypic characteristics and response to the use of recombinant human growth hormone

As alterações cromossômicas estruturais no cromossomo 14 são incomuns e podem levar a um espectro variado de manifestações clínicas, incluindo hipotonia, atraso no desenvolvimento psicomotor, déficits cognitivos e dismorfismos faciais. O fenótipo específico é influenciado pela localização, extensão e pontos de interrupção da deleção. Este relato de caso tem como objetivo detalhar o fenótipo e genótipo de uma pré-escolar com deleção 14q24.1, além de documentar a resposta ao tratamento com hormônio do crescimento recombinante humano (rhGH). A paciente, uma prematura nascida com medidas adequadas para a idade gestacional e filha de pais não consanguíneos, apresentou desconforto respiratório e dificuldades de deglutição no período neonatal, necessitando de gastrostomia até o primeiro ano de vida. Entre o nascimento e os dois anos e seis meses, ela apresentou uma redução da velocidade de crescimento e baixa estatura desproporcional. Foram observados também inclinação palpebral superior bilateral, baixa inserção das orelhas, fissura palatina posterior, dentição irregular, micrognatia, retrognatia, escoliose, encurtamento do fêmur direito com marcha antálgica, agenesia do rim esquerdo e posicionamento pélvico do rim direito. Além disso, a paciente exibiu atraso no desenvolvimento neuropsicomotor. A análise genética revelou uma deleção no braço longo do cromossomo 14 de aproximadamente 231 Kb. Com o tratamento com rhGH, observou-se melhora na taxa de crescimento e na estatura final. A evolução clínica do caso indica que a administração de rhGH, associada ao acompanhamento clínico rigoroso e ao tratamento das comorbidades, pode contribuir para a melhoria dos parâmetros antropométricos.

Structural chromosomal changes on chromosome 14 are uncommon and can lead to a diverse spectrum of clinical manifestations, including hypotonia, delayed psychomotor development, cognitive deficits, and facial dysmorphisms. The specific phenotype is influenced by the location, extent, and breakpoints of the deletion. This case report aims to detail the phenotype and genotype of a preschooler with 14q24.1 deletion, in addition to documenting the response to treatment with recombinant human growth hormone (rhGH). The patient, a premature female, born with appropriate measurements for gestational age and daughter of non-consanguineous parents, presented respiratory discomfort and swallowing difficulties in the neonatal period, requiring gastrostomy until the first year of life. Between birth and two years and six months, she presented a reduction in growth speed and disproportionate short stature. Bilateral upper eyelid tilt, low ear insertion, posterior cleft palate, irregular dentition, micrognathia, retrognathia, scoliosis, shortening of the right femur with antalgic gait, agenesis of the left kidney and pelvic positioning of the right kidney were also observed. Furthermore, the patient exhibited delayed neuropsychomotor development. Genetic analysis revealed a deletion on the long arm of chromosome 14 of approximately 231 Kb. With rhGH treatment, an improvement in growth rate and final height was observed. The clinical evolution of the case indicates that the administration of rhGH, associated with strict clinical monitoring and treatment of comorbidities, can contribute to the improvement of anthropometric parameters.

Prenatally diagnosed partial trisomy 3Q22.2→3QTER, partial monosomy 11Q25→11QTER and interstitial deletion 10Q25.1-10Q25.2: a case report and review of literature / Diagnóstico prenatal de trisomía parcial 3Q22.2→3QTER, monosomía parcial 11Q25→11QTER y deleción intersticial 10Q25.1-10Q25.2: reporte de un caso y revisión de la literatura

ABSTRACT A 19-year-old pregnant woman was admitted to our ultrasound department at 20.4 weeks of gestation. Prenatal sonography identified a fetus with trigonocephaly, an omphalocele protruding out of the abdominal wall, on the right side of the umbilical cord, that contained the liver and bowel, claw hand and bot foot. Amniocentesis revealed an unbalanced chromosome constitution 46,XX,der(11)t(3,11)(q22.2,q24.3) resulting in a deletion of 11q24.3 to 11qter and a duplication of 3q22.2 to 3qter product of a "de novo imbalanced translocation"; the parents' karyotypes were normal. The chromosome microarray results for the proband revealed a 63.07 Mb duplication in the chromosome 3 located at 3q22.2 to terminal 3q29; a 4.08 Mb deletion in the chromosome 11 located at 11q25, and a 5.66 Mb loss in the chromosome 10 located at 10q25.1 to 10q25.2. To the best of our knowledge, this is the first report of this combination of chromosomal abnormalities.

RESUMEN Una embarazada de 19 años ingresó en nuestro servicio de ultrasonido a las 20,4 semanas de gestación. La ecografía prenatal identificó un feto con trigonocefalia, un onfalocele que sobresalía de la pared abdominal, en el lado derecho del cordón umbilical, que contenía el hígado y el intestino, una mano en garra y un pie bot. La amniocentesis reveló una constitución cromosómica desequilibrada 46,XX,der(11)t(3,11)(q22.2,q24.3) que resultó en una deleción de 11q24.3 a 11qter y una duplicación de 3q22.2 a 3qter producto de una "translocación desequilibrada de novo"; los cariotipos de los padres eran normales. Los resultados del microarreglo cromosómico para el probando revelaron una duplicación de 63,07 Mb en el cromosoma 3 ubicado en 3q22.2 a terminal 3q29; una deleción de 4,08 Mb en el cromosoma 11 ubicado en 11q25 y una pérdida de 5,66 Mb en el cromosoma 10 ubicado en 10q25.1 a 10q25.2. Hasta donde sabemos, este es el primer informe de esta combinación de anomalías cromosómicas.

Study about the Genetic Variability, Heritability and Genetic Advance for Yield and Yield Attributing Traits of Brinjal (Solanum melongena L.)

Brinjal is an important vegetable crop grown in India, Asia, and many parts of the world. The primary objective of brinjal breeding is to develop varieties that are resistant to pests and diseases, have higher yields, and better fruit quality. In this study, 10 brinjal varieties were crossed to obtain F1’s hybrids. The F1’s were evaluated for yield and yield-related characters. The results showed a wide range of variation for all characters. The estimates of heritability in F1 varied from 45.43% (number of primary branches per plant) to 97.69% (Average Fruit weight). The genetic advance percent over mean for F1 varied from 6.25 % (Number of primary branches per plant) to 62.16 % (Average Fruit weight). Seven characters showed high performance viz. Average Fruit weight (62.16%) , Number of Fruit per Plant (50.37%), Fruit yield per plant (49.37), Fruit circumference (35.18), Plant height (32.77), Number of Secondary branches per plant (29.14%) and Fruit length (27.11%); three medium performance viz. Days of 50% Flowering after transplanting (18.09), Days of First Fruit harvest after transplanting (15.35) and Fruit T.S.S (11.92%); one low performance i.e., Number of primary Branches per plant (6.25%). The PCV was higher than GCV indicate the role of environment in performance of characters while value of both have narrow difference indicate the mainly genetic factors is responsible for the performance of the characters of genotypes.High heritability coupled with high genetic advance was found for yield and yield attributing characters, which indicates that selection for these traits will be effective.

¿Qué puede esconder el retraso global del desarrollo? A propósito de un caso de causa genética / What can Global Developmental Delay Conceal? Apropos of a Case with a Genetic Cause

Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)

A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)

Hemophagocytic syndrome in a patient with Fanconi anemia and VACTERL association / Síndrome hemofagocítica em paciente com anemia de Fanconi e associação VACTERL

INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

Raquitismo hipofosfatémico familiar ligado al cromosoma X: Reporte de Caso

El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.

Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.