Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.
Growth Hormone-Secreting Pituitary Adenoma ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Pituitary Neoplasms ; genetics

Humans ; Arthritis, Juvenile/genetics* ; Intracellular Signaling Peptides and Proteins/genetics* ; Genetic Predisposition to Disease

Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation ; Nephrotic Syndrome ; etiology ; genetics ; WT1 Proteins ; genetics

OBJECTIVETo investigate the role of transcript factor SCL/TAL-1 gene in the erythroid differentiation through the knockdown of SCL/TAL-1 mRNA by RNA interference.

METHODSThe plasmid of pTRIP-dU3-RNAiTALh-EF1a-GFP with SCL/TAL1 shRNA was transfected into EPO-induced K562 cell line with erythroid differentiation via lentiviral vector system and the expression of SCL/TAL-1 mRNA decreased. The plasmid pTRIP-dU3- RNAiluc-EF1-GFP expressing EGFP gene was as control. The mRNA levels of SCL/TAL-1 and erythroid related RhD, GPA, CD47 in the cell lines were detected by RT-PCR, and erythroid antigen CD71, CD235a were examined by flow cytometry.

RESULTS(1) After 48 h of transfect, more than 95% of K562 cells were GFP positive, indicating the infection rate of the plasmids in the K562 cells more than 95%. (2) The results of RT-PCR showed SCL/TAL-1 mRNA expression in the K562 cell line of knockdown of SCL/TAL-1 was significantly lower than that in the control (P < 0.05). The mRNA levels of CD47 and RhD were also significantly lower, however, GPA decreased slightly in comparison with the control. (3) The expressions of CD71 and CD235a markedly reduced in the K562 cell line of knockdown of SCL/TAL-1 with positive rates as 10.4% and 76.5%, while the positive rates in the control as 94.3% and 83.6%.

CONCLUSIONOur findings suggested that transcription factor SCL/TAL-1 might play an positive role in erythroid differentiation.

Cell Differentiation ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; K562 Cells ; RNA Interference

Adolescent ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Lymphohistiocytosis, Hemophagocytic ; genetics ; Mutation ; Signaling Lymphocytic Activation Molecule Associated Protein

Drug Resistance ; Glucocorticoids ; therapeutic use ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation ; Nephrotic Syndrome ; drug therapy ; genetics

IFIT family genes are a kind of interferon stimulated genes (ISGs), and play important roles in antiviral sector and immunity regulation. To study the regulatory effect of IFIT family genes during influenza A virus (IAV) infection, we used RNA-sequencing analysis (RNA-Seq) technique and found that when 293T cells were infected by A/WSN/33 (WSN), the concentration of IFIT family genes were increased. Further study reveals that overexpression of IFIT2 or IFIT3 could inhibit IAV replication and transcription, and cause the dose-dependent inhibition of polymerase activity of vRNP. In addition, IFIT2 and IFIT3 encoding protein could colocalize with NS1 in 293T cells infected by WSN, indicating that they might interact with each other. The results suggest that IFIT family genes can inhibit the replication and transcription of IAV, which contributes to our understanding of the regulatory effect of host factors during influenza virus infection.
HEK293 Cells ; Humans ; Influenza A virus ; physiology ; Influenza, Human ; genetics ; Intracellular Signaling Peptides and Proteins ; genetics ; Proteins ; genetics ; Virus Replication

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome (BOS). METHODS: The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes. Candidate variants were verified by Sanger sequencing of the family members. RESULTS: The proband was found to harbor a c.1627C>T (p.Gln543Ter) nonsense variant of the EYA1 gene. Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS+PP3+PP4). CONCLUSION The c.1627C>T (p.Gln543Ter) variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree. Above finding has provided a basis for its clinical diagnosis.
Branchio-Oto-Renal Syndrome ; China ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Mutation ; Nuclear Proteins/genetics* ; Pedigree ; Protein Tyrosine Phosphatases/genetics*

OBJECTIVETo identify whether SH3GL1 gene serves as a disease associated gene of adolescent idiopathic scoliosis (AIS).

METHODSPositioning candidate cloning: "case-sibling or case-family control design" research scheme based on family constellation was designed. Fifty-six AIS patients (15 male and 41 female, mean age 15 years old, ranged from 8 to 22 years old, Cobb angle from 25 degrees to 110 degrees , average Cobb angle of 67.5 degrees ) from November 2007 to December 2008 were recruited. In all patients, blood preparation was collected, and genome DNA was extracted. According to nucleotide sequence of gene SH3GL1, primer pair for PCR amplification, cloning, and sequencing with 10 exons as emphasis was designed. Sequence comparative analysis for exon sequencing result between sib pairs or family pairs, and that between sib pair or family pairs and NCBI (National Center for Biotechnology Information) were conducted through Vector NTI Advance 10.3 software to judge whether basic group mutation occurred or not. Amino acid sequence comparative analysis for prediction was made.

RESULTSTen exons of the candidate gene SH3GL1 were successfully amplified and cloned in genome DNA of an AIS sib pair and family pairs, and the sequencing obtained positive results. Twelve basic group mutations were found in 10 exons of the candidate gene SH3GL1 of patients with AIS. These mutations were located in the second exon (3 mutations), the fourth exon (1 mutations), the fifth exon (4 mutations), the sixth exon (1 mutations), the eighth exon (1 mutations), and the tenth exon (2 mutations, noncoding region). If basic group in 515 of mRNA was mutated to T, termination codon(TAG) came into being and open reading frame was altered. The sequence of protein showed brachytmema protein was encoded, which could cause changes of primary structure.

CONCLUSIONSH3GL1 is possibly one of the disease associated genes of AIS.

Adolescent ; Base Sequence ; Child ; Exons ; genetics ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Scoliosis ; genetics ; Sequence Alignment ; Young Adult

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis