OBJECTIVE: To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). METHODS: Clinical data of the child who had presented at the Zhengzhou Children's Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES) was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. RESULTS: The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of 10 patients with FHL2 gene variants have been reported in the literature, 6 of them had presented with DCM, 2 with hypertrophic cardiomyopathy (HCM), and 2 with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5). CONCLUSION The heterozygous missense variant of c.391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of WES in the clinical diagnosis and genetic counseling.
Female ; Humans ; Cardiomyopathy, Dilated/genetics* ; Cardiomyopathy, Hypertrophic ; Genetic Counseling ; Genomics ; Heterozygote ; Muscle Proteins/genetics* ; Transcription Factors ; LIM-Homeodomain Proteins/genetics*

Sexual orientation is influenced by both environmental factors and biological factors. Family and twin studies have shown that genetic factors play an important role in the formation of male homosexuality. Genome-wide scan also revealed candidate chromosomal regions which may be associated with male homosexuality, but so far no clearly related genes have been found. This article reviews the progress of relevant studies and candidate genes which are related to male homosexuality.
Animals ; Aromatase ; genetics ; Catechol O-Methyltransferase ; genetics ; Homosexuality, Male ; genetics ; Humans ; LIM-Homeodomain Proteins ; genetics ; Male ; Receptors, Dopamine D1 ; genetics ; Transcription Factors ; genetics

OBJECTIVETo investigate the association between 2 SNPs of ISL1 gene and congenital heart disease (CHD) in Tianjin Han children.

METHODSPolymerase chain reaction and DNA sequencing were used to detect 2 SNPs at rs41268421 and rs1017 sites of ISL1 gene, including 35 CHD cases and 30 non-CHD controls. Differences of genotype and allele frequencies of rs41268421 and rs1017 sites were compared, and haplotype analysis of the two sites was performed.

RESULTSThree genotypes (GG, GT and TT) were detected at ISL1 gene SNP rs41268421, and three genotypes (AA, AT and TT) were detected at SNP rs1017. At rs41268421, GT+TT genotypes and T allele frequencies in the CHD group were statistically higher than in the controls. The risk of CHD in children with T allele was significantly increased compared with children with G allele (OR=4.833). At rs1017, AT+TT genotypes and T allele frequencies in the CHD group were statistically higher than controls. The risk of CHD in children with T allele was greater compared with children with A allele (OR=4.491; P<0.05). Four kinds of haplotype were detected in the two SNPs sites and TT type increased the risk of CHD (OR=7.813).

CONCLUSIONSHaplotype TT may increase the risk of CHD in Tianjin Han children.

Child, Preschool ; Female ; Genotype ; Haplotypes ; Heart Defects, Congenital ; genetics ; Humans ; Infant ; LIM-Homeodomain Proteins ; genetics ; Male ; Polymorphism, Single Nucleotide ; Transcription Factors ; genetics

OBJECTIVETo construct a recombiant lentivirus vector of human LMP-1 and detect the expression of LMP-1 in infected rat bone mesenchymal stem cells.

METHODSLMP-1 gene from the cDNA library were extracted by Polymerase Chain Reaction (PCR). The LMP-1 genes were connected into lentiviral vectors pGC-FU-EGFP which was linearized by Age I enzyme to produce recombiant lentivirus vector called as pGC-FU-LMP-1-EGFP,then packaged by 293T cells. The virus supernant congtaining LV-LMP-1-EGFP was harvested, concentrated and titrated. The rat BMSCs were transfected with recombiant lentivirus LV-LMP-1-EGFP at the most appropriate MOI. The mRNA and protein expression of LMP-1 were detected by RT-PCR and Western blot.

RESULTS1LV-LMP-1I-EGFP was recombined successfully and the titer reached 2x108TU/ml. 2The efficiency of infection was 93.5% ,which was get after LV-LMP-1-EGFP infected rat BMSCs at the most appropriate MOI=100. The expression of LMP-1 gene was confirmed by RT-PCR and Western blot.

CONCLUSIONLentivirus vector containing human LMP-1 gene is constructed successfully,which can transfected efficiently into rat BMSCs,and the infected rat BMSCs can effectively express LMP-1.

Animals ; Female ; Genetic Vectors ; LIM-Homeodomain Proteins ; genetics ; Lentivirus ; genetics ; Male ; Mesenchymal Stromal Cells ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; genetics ; Transfection

OBJECTIVETo investigate the expression of transcription regulator LMO4 mRNA in the developing mouse molar and compare the expression pattern of LMO4 with that of Shh signaling molecule.

METHODSWild-type embryos used in this study (E11.5-P1.5) were generated by mating Kun-Ming mice. The expression pattern of LMO4 during organ development was carried on by whole-mount in situ hybridization. The expression patterns of LMO4 and Shh mRNA during molar development were analysed by section in situ hybridization. Immunohistochemical staining of PCNA was carried on by SP method.

RESULTSLMO4 mRNA was widespread at early embryonic stages (E11.5) with positive hybridization signal in the mandibular reason, limb bud, brain, epidermis and somites revealed by whole-mount in situ hybridization. Section in situ hybridization showed that LMO4 was expressed in the tooth bud, the two tips of the enamel organ and the cervical loop from E13.5 to E16.5. While Shh was localized in the enamel knot on E14.5. On E18.5-P1.5, LMO4 transcripts were distributed in the ameloblast and the stratum intermedium. On E13.5-E16.5, the tooth bud cells and the cervical loop cells were PCNA positive. These were the same regions that showed LMO4 mRNA expression.

CONCLUSIONSLMO4 was confined to the dental epithelium and had spatial temporal expression patterns during tooth morphogenesis. The expression patterns of LMO4 and Shh were similar. In early tooth development, LMO4 might regulate cell proliferation. In late tooth development, it might participate in the ameloblast differentiation.

Adaptor Proteins, Signal Transducing ; Animals ; Animals, Newborn ; Female ; Gene Expression Regulation, Developmental ; Homeodomain Proteins ; biosynthesis ; LIM Domain Proteins ; Mice ; Mice, Inbred Strains ; Morphogenesis ; genetics ; Pregnancy ; Tooth Germ ; metabolism ; Transcription Factors ; biosynthesis ; Transcription, Genetic

BACKGROUNDId3 plays a key role in the progression of breast cancer. Previously, four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them. This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells.

METHODSCell transfection was performed with SuperFect reagent. Stable transfectants that overexpressed Id3 were obtained by selection on G418. The level of Id3 protein was determined by Western blotting analysis. Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells. The MTT assay was used to measure cell proliferation. The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells.

RESULTSId3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells. This Id3-mediated repression was effectively antagonized by FHL2. Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however, these effects were significantly suppressed by the overexpression of FHL2.

CONCLUSIONSFHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3. The functional roles of FHL2-Id3 signaling in the development of human breast cancer need further research.

Blotting, Western ; Breast Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Inhibitor of Differentiation Proteins ; genetics ; metabolism ; LIM-Homeodomain Proteins ; genetics ; metabolism ; MCF-7 Cells ; Muscle Proteins ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Transcription Factor 3 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism

OBJECTIVETo investigate the association of prostate cancer (PCa) with PDLIM5 (rs17021918, T), SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) in Chinese men.

METHODSWe included 124 PCa patients and 138 normal controls in this study, compared the alleles and genotypes of PDLIM5 (rs17021918, T) , SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) of the two groups, and explored the association of each of the genes with the age, body mass index (BMI), Gleason score, PSA level and tumor stage of the patients. We analyzed the gene-gene interaction using the multifactor dimensionality reduction method (MDR).

RESULTSThere were no statistically significant differences in the frequency distribution of the risk alleles and genotypes of PDLIM5, SLC22A3 and NKX3-1 between the case and control groups (P > 0.05), nor were the three gene loci significantly associated with the age, Gleason score, PSA level and pathological grade of the PCa patients (CP < 0.05). MDR analysis showed no interaction between PDLIM5 and NKX3-1, but tree-diagram analysis revealed a possible synergistic action of the two polymorphism loci.

CONCLUSIONPCa might not be associated with PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) in Chinese men. However, PDLIM5 and NKX3-1 might have a synergistic action on the risk PCa.

Adaptor Proteins, Signal Transducing ; genetics ; Aged ; Aged, 80 and over ; Alleles ; Case-Control Studies ; Genotype ; Homeodomain Proteins ; genetics ; Humans ; LIM Domain Proteins ; genetics ; Male ; Middle Aged ; Organic Cation Transport Proteins ; genetics ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms ; genetics ; Risk Factors ; Transcription Factors ; genetics

Steroid-resistant nephrotic syndrome poses a significant clinical challenge. Its pathogenesis has not been fully elucidated. In recent years, numerous studies have shown that podocyte-specific gene mutations may play important roles in the development of steroid-resistant nephrotic syndrome. Among the identified genes mutated in podocytes include NPHS2, NPHS1, WT1, TRPC6, MDR1, PLCE1, LMX1B, and LAMB2. This review aims to summarize the characteristics of these mutated genes in podocytes. The putative role for these podocyte-specific mutated genes in the pathogenesis, diagnosis, treatment and prognosis of steroid-resistant nephrotic syndrome is also discussed.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Genes, Wilms Tumor ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; LIM-Homeodomain Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation ; Nephrotic Syndrome ; congenital ; genetics ; Podocytes ; metabolism ; TRPC Cation Channels ; genetics ; TRPC6 Cation Channel ; Transcription Factors ; genetics