Tamoxifen resistance remains a significant therapeutic challenge in estrogen receptor-positive (ERα+) breast cancer. Although arginine metabolic reprogramming has been recognized as a driver of tumor progression, its role in tamoxifen resistance is not well understood. In this study, we demonstrate that the arginine-metabolizing enzyme ARG2 and its metabolite spermine are significantly elevated in tamoxifen-resistant cells. High ARG2 expression correlates with poor prognosis in ERα + patients. Silencing ARG2 genetically or inhibiting spermine synthesis pharmacologically using difluoromethylornithine (DFMO) effectively re-sensitizes resistant tumors to tamoxifen in vitro and in vivo. Mechanistically, we demonstrated that spermine inhibits apoptosis by suppressing the cleavage of Caspase2, revealing a previously unrecognized anti-apoptotic mechanism in resistant cells. Additionally, we revealed that POLR3A, a RNA polymerase III subunit, transcriptionally activates ARG2 expression, representing a non-canonical transcriptional function of POLR3A in cancer. In conclusion, this study establishes the POLR3A/ARG2/spermine axis as a critical driver of tamoxifen resistance and reveals a non-canonical transcriptional function of POLR3A. Importantly, our findings suggest DFMO, an existing anti-parasitic agent, as a promising combination therapeutic option for tamoxifen-resistant breast cancer.

Protein profiles of amniotic fluid extracellular vesicle-enriched preparations may provide information on the fetal and gestational intrauterine environment, but their normal variation remains incompletely characterized. We used data-independent acquisition-based quantitative proteomics to compare AF-EV-enriched preparations sampled at approximately 19 and 24 weeks from pregnancies with normal fetal cytogenetic findings and uncomplicated outcomes. Of 3321 quantified proteins, 2611 detected in at least three of four samples in each group were included in the primary analysis without imputation. Primary analysis identified 904 candidates. Of these, 698 were also supported by the KNN sensitivity analysis with concordant direction, including 385 higher at 19 W and 313 higher at 24 W. A separate complete-case analysis identified 596 candidates, all within the 698-protein set. Nominal over-representation analysis using the 2611 eligible protein groups as the background highlighted metabolic/digestion and apical/brush-border annotations among 19 W-higher candidates and proteasome-centered annotations among 24 W-higher candidates. These enrichment findings are exploratory because the displayed P values were not adjusted for multiple comparisons. Given the small cohort and absence of independent validation and comprehensive EV characterization, the results are hypothesis-generating and cannot establish EV-specific gestational remodeling. SIGNIFICANCE: Gestational age is a recognized source of variation in total amniotic fluid, but its influence on proteins recovered from AF-EV-enriched preparations during mid-pregnancy is less well defined. Using DIA proteomics, we compared preparations sampled at approximately 19 and 24 weeks from pregnancies with normal fetal cytogenetic findings and uncomplicated outcomes. Of 3321 quantified proteins, 698 were supported by both the primary analysis and KNN sensitivity analysis and were retained as hypothesis-generating candidates. Nominal over-representation analysis using the 2611 protein groups eligible for the primary analysis as the background highlighted metabolic/digestion and apical/brush-border annotations among 19 W-higher candidates and proteasome-centered annotations among 24 W-higher candidates. These unadjusted enrichment results are descriptive and do not establish EV-specific remodeling. The findings nevertheless indicate that gestational age should be considered when designing and interpreting AF-EV proteomic studies and provide candidates for validation in larger independent cohorts.

Amniotic fluid exosomes (AF-Exos) are pivotal carriers of biological information during fetal development; however, their role in 22q11.2 Deletion Syndrome (22q11.2DS) remains unclear. To elucidate the molecular mechanisms underlying fetal anomalies in 22q11.2DS, this study performed a comprehensive multiomics analysis of AF-Exos obtained from 22q11.2DS fetuses (n = 5) and matched controls (n = 5). While exosomal morphology and size distribution remained unaltered, integrated lipidomic and proteomic profiling revealed profound molecular remodeling. Lipidomics analysis revealed a specific suppression of diacylglycerols, triacylglycerols, and ceramides, accompanied by a shift in carbon chain length distribution. Concurrently, data-independent acquisition proteomics identified 329 differentially expressed proteins, highlighting a significant downregulation of PI4KA and widespread perturbations in pathways governing cardiovascular morphogenesis, angiogenesis, and SNARE-mediated vesicular transport. Integrated network analysis revealed strong correlations between the depletion of key lipids and reduced abundance of PI4KA and SNARE complex components, suggesting a potential interplay between lipid metabolism and vesicle trafficking. These findings, extending beyond the primary genetic driver TBX1, point to distinct alterations in lipid signaling and exosomal transport machinery in 22q11.2DS, suggesting a novel parallel pathogenic mechanism. This study provides a novel multiomics resource for understanding 22q11.2DS pathogenesis and generates valuable hypothesis-driven candidates for future mechanistic investigation.

OBJECTIVE:To investigate the steady-state mechanism of interconversion between the SMN1 and SMN2 genes in a normal population. METHODS:Fluorescence PCR capillary electrophoresis was employed to assess gene conversion and copy number variation of SMN1 and SMN2 in a cohort of 1,133 healthy individuals (including 256 males and 877 females) recruited between 2019 and 2023. This study was approved by the Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2019-134). RESULTS:No significant gender difference was observed in the single copy carrying rate of SMN1. The probability of conversion from SMN1 to SMN2 was determined to be 3.2% for females, 2.7% for males, and 3.1% for the overall population. The probability of conversion from SMN2 to SMN1 was found to be 5.5% for females, 6.3% for males, and 5.6% for the overall population. No statistically significant difference was found in the conversion probability between different genders (P > 0.05). Among the 99 cases of gene conversion, the SMN1 gene predominantly exhibited a copy number of 2 (97.0%), with the remainder having 3 copies (3%). The SMN2 gene primarily showed a copy number of 2 (72.7%), with the rest having 1 copy (27.3%). CONCLUSION:Gene conversion tends to normalize the copy numbers of both SMN1 and SMN2 genes towards 2. However, SMN1 exhibited a higher priority over SMN2, causing the copy numbers approaching two.

Background: The MTHFR 677C > T polymorphism in women has been associated with an increased risk of deep venous thrombosis and adverse pregnancy outcomes (APOs). However, research concerning its effects in men remains limited. Methods: This study examined 662 adults with a history of pregnancies affected by chromosomal abnormalities (CAs: 343 females and 319 males), 137 adults with a history of pregnancies affected by cleft lip and palate (CLP: 71 females and 66 males), and 133 adults with a history of biochemical pregnancies (BPs: 65 females and 68 males), forming three case groups. A control group of 339 adults without APOs (221 females and 118 males) was studied. The genotypes of the MTHFR 677C > T polymorphism and Hcy levels were analyzed for all participants. Results: Elevated Hcy levels were identified as a risk factor for CA, CLP, and BP in both adult females and males. The MTHFR 677C > T polymorphism was a risk factor for CA, CLP, and BP in females, whereas in males, it was a risk factor for CA and BP, but not for CLP. Individuals with the TT genotype exhibited the highest Hcy levels compared to those with CC and CT genotypes, across both genders and all groups. Males exhibited significantly higher Hcy levels and a significantly greater incidence of hyperhomocysteinemia compared to females across all groups. Conclusions: The MTHFR 677C > T polymorphism was a gender-dependent risk factor for fetal CLP but was gender-independent for BP and fetal CA. Elevated Hcy levels were a gender-independent risk factor for BP, CLP, and CA. Individuals with the MTHFR 677TT genotype were more likely to have elevated Hcy levels, and there were notable gender differences in Hcy levels and hyperhomocysteinemia incidence.

Down syndrome (DS) is the most example of aneuploidy, resulting from an additional copy of all or part of chromosome 21. Competing endogenous RNAs (ceRNAs) play important roles in neuronal development and neurological defects. This study aimed to identify hub genes and synergistic crosstalk among ceRNAs in the DS fetal hippocampus as potential targets for the treatment of DS-related neurodegenerative diseases. We profiled differentially expressed long non-coding RNAs (DElncRNAs), differentially expressed circular RNAs (DEcircRNAs), differentially expressed microRNAs (DEmiRNAs), and differentially expressed messenger RNAs (DEmRNAs) in hippocampal samples from patients with or without DS. Functional enrichment analysis and gene set enrichment analysis were performed, and chromosome 21-related ceRNA and protein–protein interaction networks were constructed. Additionally, the correlations between lncRNA-mRNA and miRNA-mRNA expression in the samples and HEK293T cells were validated. Our finding of changes in the expression of some key genes and ncRNAs on chromosome 21 in DS might not fully conform to the gene dosage hypothesis. Moreover, we found that four lncRNAs (MIR99AHG, PLCB4, SNHG14, GIGYF2) and one circRNA (hsa_circ_0061697) may competitively bind with three miRNAs (hsa-miR-548b-5p, miR-730-5p, and hsa-miR-548i) and subsequently regulate five mRNAs (beta-1,3-galactosyltransferase 5 [B3GALT5], helicase lymphoid-specific [HELLS], thrombospondin-2 [THBS2], glycinamide ribonucleotide transformylase [GART], clathrin heavy chain like 1 [CLTCL1]). These RNAs, whether located on chromosome 21 or not, interact with each other and might activate the PI3K/Akt/mTOR and Wnt signaling pathways, which are involved in autophagosome formation and tau hyperphosphorylation, possibly leading to adverse consequences of trisomy 21. These findings provide researchers with a better understanding of the fundamental molecular mechanisms underlying DS-related progressive defects in neuronal development.

Purpose Exploring the connection between Hashimoto's thyroiditis (HT) and non-alcoholic fatty liver disease (NAFLD) through integrated genetic approaches. Methods We utilized integrated genetic approaches, such as single-cell RNA sequencing (scRNA-seq) data analysis, Mendelian Randomization (MR), colocalization analysis, cell communication, and metabolic analyses, to investigate potential correlations between HT and NAFLD. Results Through the integrated analysis of scRNA-seq data from individuals with HT, NAFLD, and healthy controls, we observed an upregulation in the proportion of CD4(+)central memory (CD4(+)CM) T cells among T cells in both diseases. A total of 63 differentially expressed genes (DEGs) were identified in the CD4(+)CM cells after the differential analysis. By using MR, 8 DEGs (MAGI3, CSGALNACT1, CAMK4, GRIP1, TRAT1, IL7R, ERN1, and MB21D2) were identified to have a causal relationship with HT, and 4 DEGs (MAGI3, RCAN3, DOCK10, and SAMD12) had a causal relationship with NAFLD. MAGI3 was found to be causally linked to both HT and NAFLD. Therefore, MAGI3 was designated as the marker gene. Reverse MR and Steiger filtering showed no evidence of reverse causality. Colocalization analyses further indicated close links between MAGI3 and HT as well as NAFLD. Finally, based on the expression levels of MAGI3, we stratified CD4(+)CM cells into two subsets: MAGI3(+)CD4(+)CM cells and MAGI3(-)CD4(+)CM cells. Functional analyses revealed significant differences between the two subsets, potentially related to the progression of the two diseases. Conclusion This study delves into the potential connections between HT and NAFLD through integrated genetic methods. Our research reveals an elevated proportion of CD4(+)CM cells within T cells in both HT and NAFLD. Through MR and colocalization analysis, we identify specific genes causally linked to HT and NAFLD, such as MAGI3. Ultimately, based on MAGI3 expression levels, we categorize CD4(+)CM cells into MAGI3(+)CD4(+)CM cells and MAGI3-CD4(+)CM cells, uncovering significant differences between them through functional analyses.

The E3 ligase MDM2 promotes tumor growth and progression by inducing ubiquitin-mediated degradation of P53 and other tumor-suppressing proteins. Here, we identified an MDM2-interacting lncRNA NRON, which promotes tumor formation by suppressing both P53-dependent and independent pathways. NRON binds to MDM2 and MDMX (MDM4) via two different stem-loops, respectively, and induces their heterogenous dimerization, thereby enhancing the E3 ligase activity of MDM2 toward its tumor-suppressing substrates, including P53, RB1, and NFAT1. NRON knockdown dramatically inhibits tumor cell growth in vitro and in vivo. More importantly, NRON overexpression promotes oncogenic transformation by inducing anchorage-independent growth in vitro and facilitating tumor formation in immunocompromised mice. Clinically, NRON expression is significantly associated with poor clinical outcome in breast cancer patients. Together, our data uncover a pivotal role of lncRNA that induces malignant transformation of epithelial cells by inhibiting multiple tumor suppressor proteins.

This study is to identify the pathogenic mutation of a child with Sots syndrome and provide prenatal diagnosis for his pregnant mother. Chromosome microarray technology was used to detect whether there were minor deletions/duplication in patients’ chromosomes. The gene mutation of patients was screened by next-generation sequencing technology, and it was verified by Sanger sequencing. Prenatal diagnosis of the fetus was conducted according to the selected pathogenic sites, and genetic counseling was conducted for her parents. Chromosome microarray results showed that there was no minor deletion in a chromosome 5q35 region, and the second-generation sequencing results showed that there was a c.4138delG heterozygous mutation in the patient’s NSD1 gene, and the pathogenic of this mutation was not reported in related databases. Sanger sequencing found that there was a c.4138delG heterozygous mutation in the NSD1 gene of the patient and her parents’ genotype at this locus was wild type. The prenatal gene test results indicated that there was heterozygous mutation of NSD1 gene c.4138delG in the fetus, so it was suggested to terminate the pregnancy. Gentling results indicated that the fetus and the patient inherited the same maternal chromosome 5. The heterozygous mutation of NSD1 gene c.4138delG is the pathogenic mutation of this Sots syndrome patient, and the mother may be germinal mosaicism.

Research question: Do maternal homocysteine (Hcy) concentrations, MTHFR and MTRR genes have effects on the occurrence of fetal aneuploidy?Design: A total of 619 aneuploidy mothers and 192 control mothers were recruited in this study. Differences in distributions of maternal MTHFR 677C>T, MTHFR 12 98A>C and MTRR 66A>G genetic polymorphisms and maternal Hcy concentrations between aneuploidy mothers and control mothers were analysed.Results: The maternal MTHFR 67 7C>T polymorphism was found to be a risk factor for the occurrence of many fetal non -mosaic aneuploidies studied here, including trisomies 13, 15, 16, 18, 21, 22, TRA and TS. The maternal MTHFR 12 98A>C polymorphism was found to be a risk factor specifically associated with the occurrence of fetal trisomy 15 and fetal TS. The maternal MTRR 66A>G polymorphism was found to be a risk factor only specifically associated with the occurrence of fetal trisomy 21. The Hcy concentrations of mothers of trisomies 22, 21, 18, 16, 15 and TS fetuses were significantly higher than the Hcy concentrations of control mothers.Conclusions: Overall, data suggested an association between these maternal polymorphisms and the susceptibility of fetal non-mosaic trisomy and Turner syndrome. However, these three maternal polymorphisms had different associations with the susceptibility of different fetal aneuploidies, and the elevated maternal Hcy concentration appeared to be a likely risk factor for fetal Turner syndrome and fetal trisomies.

Around the whole world, smoking is considered harmful to human health, such as increasing the risk of cardiovascular disease (CVD, such as coronary heart disease and stroke) and lung cancer. The purpose of this study was to explore whether nicotine, the main component of tobacco, has adverse effects on heart rate variability (HRV) in adolescents, so as to remind adolescents not to smoke and not to take pleasure in abusing nicotine. In this study, 40 male and 40 female young healthy nonsmoking subjects were selected to analyze the changes of HRV after taking 4 mg nicotine orally. We found that nicotine reduced HRV in young healthy male and female subjects, and there was no gender difference in this effect (P > 0.05). In conclusion, smoking is harmful to the cardiac system of young people, especially when nicotine content ≥4 mg dosage.

Objective:To explore the genetic etiology for a child featuring mental retardation and speech delay.Methods:Clinical data of the child was collected. DNA was extracted from peripheral blood samples of the child and members of his pedigree. Whole exome sequencing was carried out for the child, and candidate variants were verified by Sanger sequencing. Prenatal diagnosis was provided for his mother upon her subsequent pregnancy.Results:The child has mainly featured mental retardation, speech delay, ptosis, strabismus, photophobia, hyperactivity, and irritability. Whole exome sequencing revealed that he has harbored a pathogenic heterozygous variant of the KAT6A gene, namely c. 5314dupA (p.Ser1772fs*20), which was not detected in either of his parents. The child was diagnosed with Arboleda-Tham syndrome. The child was also found to harbor a hemizygous c. 56T>G (p.Leu19Trp) variant of the AIFM1 gene, for which his mother was heterozygous and his phenotypically normal maternal grandfather was hemizygous. Pathogenicity was excluded. Prenatal diagnosis has excluded the c. 5314dupA variant of the KAT6A gene in the fetus. Conclusion:The heterozygous c. 5314dupA (p.Ser1772fs*20) variant of the KAT6A gene probably underlay the Arboleda-Tham syndrome in this child. Above finding has enabled genetic counseling and prenatal diagnosis for this pedigree.

目的 对1例具有先天性心脏病合并特殊面容和发育迟缓的患儿进行基因诊断.方法 对患儿进行外周血全基因组拷贝数变异(CNV)检测和全外显子测序检测.结果 患儿外周血全外显子测序显示,KMT2D基因存在c.7168_c.7169 del CC杂合突变且患儿母亲和父亲均未检测到此突变,该突变符合由KMT2D基因突变导致的常染色体显性遗传病——歌舞伎综合征(KS)的发病机制;根据美国遗传学和基因组学学会指南并结合突变影响和患儿临床症状的综合分析判定该变异符合"致病突变"且与患儿临床症状相符;经ClinVar和HGMD等数据库搜索未发现此突变的记载,此突变为未曾报道过的新致病突变.患儿外周血全基因组CNV检测显示,未发现临床明确致病或可疑致病的CNV变异.结论 患儿为KMT2D基因新发突变导致的KSⅠ型.

Objective:To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening.Methods:7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down’s serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up.Results:Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV(P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively, and showing no significant difference ( χ2=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference ( χ2=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities ( χ2=1.504, P=0.22). The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. Conclusion:Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down’s serological screening.

Objective:To summarize and analyze the risk of pregnancy recurrence of women with Duchenne muscular dystrophy (DMD) birth history in families with new DMD gene mutations, clarify the laws of DMD gene mutations and discuss the mode of genetic counseling in such families.Methods:Collected DMD families from January 2013 to December 2017 in Henan Provincial People′s Hospital. Firstly, the 79 exons of DMD gene were analyzed by multiplex ligation-dependent probe amplification (MLPA) in DMD patients and their mothers. The families that DMD patients with DMD gene mutations but no mutations in their mothers were selected for this study, and then MLPA combined with STR-gene linkage analysis were used to perform prenatal diagnosis for females in these DMD gene new mutation families.Results:A total of 64 families with new DMD gene mutations were included in this study. All mutations were DMD gene exon deletion mutations. A total of 65 fetuses were conducted prenatal diagnosis, included 26 SRY negative, 39 SRY positive; 63 fetuses′ DMD gene normal and 2 fetues′ DMD gene with exon deletion mutations. The results of postpartum follow-up and prenatal diagnosis were consistent.Conclusions:Exon mutations in newly mutated DMD families were mainly manifested as exon deletion, mainly presented in the 45-55 exon region. For families with new DMD mutations, even if there is no DMD gene mutation in women which had reproductive history of DMD, prenatal diagnosis for DMD during pregnancy was still recommended.

Objective To carry out genetic testing and prenatal diagnosis for 90 families affected with spinal muscular atrophy (SMA),and discuss the necessity for carrier screening.Methods All families were subjected to multiplex ligation-dependent probe amplification (MLPA) analysis.Combined MLPA and allele-specific PCR (AS-PCR) was used for prenatal diagnosis of the pregnant women.Results Among the 90 couples,84 (93％) had a negative family history,85 (94％) had given birth to an affected child before.Eighty-five husbands and 88 wives carried heterozygous deletion of exon 7 of the SMN1 gene.Two wives had homozygous deletion of exon 7 of the SMN1 gene and were affected.Prenatal diagnosis showed that 19 fetuses were SMA patients,48 fetuses were carriers,and 23 fetuses were normal.Of note,eighteen affected fetuses were conceived by couples without a family history,which accounted for 20％ of all pregnancies and 95％ of all affected fetuses.Conclusion To screen SMA carriers using MLPA and carry out prenatal diagnosis using combined MLPA and AS-PCR can ensure accurate diagnosis,which has a significant value for the prevention of SMA affected births.

OBJECTIVE:To carry out genetic testing and prenatal diagnosis for a family affected with Duchenne muscular dystrophy (DMD).METHODS:Multiplex ligation dependent probe amplification (MLPA) was used to detect potential deletion and duplication of the Dystrophin gene. Haplotype analysis was performed using five short tandem repeat polymorphism loci (3'-STR, 5'-STR, 45-STR, 49-STR, 50-STR of the DMD gene.RESULTS:A same deletional mutation (exons 51-55) of the DMD gene was detected in two brothers but not in their mother. The patients and fetus have inherited different haplotypes of the Dystrophin gene from their mother, suggesting that the fetus was unaffected.CONCLUSION:The mother was very likely to harbor germline mosaicism for the Dystrophin gene variant. Genetic testing of peripheral blood samples cannot rule out germline mosaicism in the mother. Prenatal diagnosis should be provided for subsequent pregnancies in this family.

The role of long non-coding RNA (lncRNA) in the progression of Nasopharyngeal carcinoma (NPC) has not been fully elucidated. The study was designed to explore the functional role of NKILA, a newly identified lncRNA, in the progression of NPC. We performed a lncRNA expression profile microarray using four NPC and paired para-cancerous tissues. NKILA was identified as a potential functional lncRNA by this lncRNA expression profile. We used 107 paraffin-embedded NPC tissues with different TNM stages to detect the expression of NKILA and analyzed the survival data by Log-rank test and Cox regression. The role of NKILA and its underlying mechanisms in the progression of NPC were evaluated by a series of experiments in vitro and vivo by silencing or expressing NKILA. Compared with control tissues, NKILA expression was identified to be decreased in NPC tissues. Low NKILA expression was correlated with unfavorable clinicopathological features and predicted poor survival outcome in NPC patients. After adjusting for potential confounders, low expression of NKILA was confirmed to be an independent prognostic factor correlated with poor survival outcomes. Furthermore, we found that NKILA overexpression in high-metastatic-potential NPC cells repressed motile behavior and impaired the metastatic capacity in vitro and in vivo. In contrast, RNAi-mediated NKILA depletion increased the invasive motility of cells with lower metastatic potential. Further experiments demonstrated that NKILA regulated the metastasis of NPC through the NF-κB pathway. Taken together, NKILA plays vital roles in the pathogenesis of NPC. The unique histological characteristics of NPC indicate that local inflammation plays a vital role in carcinogenesis of nasopharyngeal carcinoma.

OBJECTIVE:To carry out genetic testing for a family affected with distal hereditary motor neuronopathy V (dHMN V).METHODS:Potential mutations of the GARS and BSCL2 genes were analyzed with PCR and Sanger sequencing. Suspected mutation was verified among unaffected members of the family and 100 healthy controls. Prenatal diagnosis was provided based on the above results.RESULTS:Sequencing analysis has identified a heterozygous c.269C>T (p.S90L) mutation in the BSCL2 gene, which resulted in replacement of Serine (TCG) to Leucine (TTG). The same mutation was found in all other 3 patients from the pedigree but not among unaffected members or the 100 healthy controls. By prenatal diagnosis, the fetus did not carry the above mutation.CONCLUSION:Pathogenic mutation of BSCL2 gene probably underlies the dHMN V in this pedigree, which enabled prenatal diagnosis for the proband.

OBJECTIVE:To provide genetic testing for two brothers with mental retardation and epilepsy.METHODS:Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree.RESULTS:A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather.CONCLUSION:The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.