AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duc...AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duct agenesis.METHODS:The members of the three families were recruited.The ophthalmologic examinations in details,including slit-lamp biomicroscope,intraocular pressure and fundus examination,etc.were carried out.All patients were checked with paracentesis of puncta membrane and lacrimal duct probing,as well as the computed tomographydacryocystography(CT-DCG).Peripheral blood of 14 participants(3 normal)from three families were collected,4 mL each,for genomic DNA extraction,and 11 exon fragments of IGSF3 gene were amplified and sequenced by polymerase chain reaction(PCR)to determine whether there were IGSF3 genetic variation.RESULTS:A total of 14 members from three families were screened for 4 synonymous variants:c.930 C>T(p.Pro366=),c.1359 T>C(p.Ser709=),c.1797 G>A(p.Ser855=),c.1539 G>A(p.Ser769=),and 6 missense variants:c.l507 G>A(p.Gly759 Ser),c.1783 T>C(p.Trp851 Arg),c.1952 G>T(p.Ser 907 lle),c.3120 C>G(p.Asp1040 Glu),c.3123 C>G(p.Asp1041 Glu),c.3139_3140 insGAC(p.Asp1046_Pro1047 insAsp),and the latter three were only found in two patients with absence of lacrimal puncta and canaliculi combined with congenital osseous nasolacrimal canal obstruction from the first family.CONCLUSION:The same IGSF3 gene mutation c.31393140 insGAC is found in the patients with congenital absence of lacrimal puncta and canaliculi combine with osseous nasolacrimal canal obstruction.展开更多
A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal p...A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.展开更多
BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism diso...BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.展开更多
Immunoglobulin superfamily(IgSF)members account for a large proportion of cell adhesion molecules that perform important immunological functions,including recognizing a variety of counterpart molecules on the cell sur...Immunoglobulin superfamily(IgSF)members account for a large proportion of cell adhesion molecules that perform important immunological functions,including recognizing a variety of counterpart molecules on the cell surface or extracellular matrix.The findings that CD155/poliovirus receptor(PVR)and CD112/nectin-2 are the ligands for CD226/platelet and T-cell activation antigen 1(PTA1)/DNAX accessory molecular-1(DNAM-1),CD96/tactile and Washington University cell adhesion molecule(WUCAM)and that CD226 is physically and functionally associated with lymphocyte function-associated antigen-1(LFA-1)on natural killer(NK)and activated T cells have largely expanded our knowledge about the functions of CD226,CD96,WUCAM and LFA-1 and their respective ligands,CD155,CD112,intercellular adhesion molecule(ICAM)-1 and junctional adhesion molecule(JAM)-1.The interactions of these receptors and their ligands are involved in many key functions of immune cells including naive T cells,cytotoxic T cells,NK cells,NK T cells,monocytes,dendritic cells,mast cells and platelets/megakaryocytes.展开更多
Proteins of the immunoglobulin superfamily (IgSF) are involved in a variety of spe- cific cell-cell interactions in the developing nervous system. To identify and characterize new members of this protein family in hum...Proteins of the immunoglobulin superfamily (IgSF) are involved in a variety of spe- cific cell-cell interactions in the developing nervous system. To identify and characterize new members of this protein family in human nervous system, we screen the human fetal brain cDNA library and isolate a full-length cDNA clone which contains a 1032 bp open reading frame en- coding a protein of 344 amino acids. Sequence analysis reveals that it is a glycoprotein com- prised of three C2-1ike immunoglobulin domains and is anchored to the plasma membrane via a post-translationally attached glycosyl-phosphatidylinositol (GPI) moiety. The protein shows high sequence similarity to the rat Ntm (97%), so we term it human neurotrimin (NTM). Northern blot analysis reveals that (HUMAN)NTM has three different transcripts with the length of 3.2 kb, 4.0 kb and 9.0 kb respectively. It has a wider expression pattern than that of (RAT) Ntm. Notably, the expression of NTM in fetal brain is higher than that in mature brain and is stronger in nervous tumors than that in normal brain tissues. We insert an HA epitope tag between the third Ig-like domain of NTM and the site of GPI attachment, then construct it into the eukaryotic expression vector pcDNA3.1+/Zeocin. The pcDNA3.1-HA-NTM is transfected into the Chinese Hamster Ovary (CHO) cells. The results demonstrate that HA-NTM is expressed on the surface of CHO cells and could strengthen the aggregation of CHO-NTM cells.展开更多
基金Supported by High-Level Talents Training Foundation of the Armed Police Force(No.GCCRC-02)。
文摘AIM:To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi,and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duct agenesis.METHODS:The members of the three families were recruited.The ophthalmologic examinations in details,including slit-lamp biomicroscope,intraocular pressure and fundus examination,etc.were carried out.All patients were checked with paracentesis of puncta membrane and lacrimal duct probing,as well as the computed tomographydacryocystography(CT-DCG).Peripheral blood of 14 participants(3 normal)from three families were collected,4 mL each,for genomic DNA extraction,and 11 exon fragments of IGSF3 gene were amplified and sequenced by polymerase chain reaction(PCR)to determine whether there were IGSF3 genetic variation.RESULTS:A total of 14 members from three families were screened for 4 synonymous variants:c.930 C>T(p.Pro366=),c.1359 T>C(p.Ser709=),c.1797 G>A(p.Ser855=),c.1539 G>A(p.Ser769=),and 6 missense variants:c.l507 G>A(p.Gly759 Ser),c.1783 T>C(p.Trp851 Arg),c.1952 G>T(p.Ser 907 lle),c.3120 C>G(p.Asp1040 Glu),c.3123 C>G(p.Asp1041 Glu),c.3139_3140 insGAC(p.Asp1046_Pro1047 insAsp),and the latter three were only found in two patients with absence of lacrimal puncta and canaliculi combined with congenital osseous nasolacrimal canal obstruction from the first family.CONCLUSION:The same IGSF3 gene mutation c.31393140 insGAC is found in the patients with congenital absence of lacrimal puncta and canaliculi combine with osseous nasolacrimal canal obstruction.
文摘A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type Ⅰ transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig Ⅴ-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.
文摘BACKGROUND Kallmann syndrome(KS)is a hypogonadotropic hypogonadism accompanied by anosmia or hyposmia.It is associated with the low secretion of gonadotropins which can lead to other abnormal endocrine metabolism disorders such as diabetes.Through genetic and molecular biological methods,more than 10 KS pathogenic genes have been found.AIM To identify the existing mutation sites of KS with diabetes and reveal the relationship between genotype and phenotype.METHODS We studied KS pathogenesis through high-throughput exome sequencing on four diabetes’patients with KS for screening the potential pathogenic sites and exploring the genotype-phenotype correlation.Clinical data and peripheral blood samples were collected from the patients.White blood cells were separated and genomic DNA was extracted.High-throughput sequencing of all exons in the candidate pathogenic genes of probands was performed,and the results obtained were analyzed.RESULTS Sequencing revealed mutations in the KLB p.T313M,ANOS1 p.C172F,and IGSF10 gene(p.Lys1819Arg and p.Arg1035Thr)at different sites,which may have been associated with disease onset.CONCLUSION The diagnosis of KS is challenging,especially in early puberty,and the clinical manifestations reflect physical delays in development and puberty.Timely diagnosis and treatment can induce puberty,thereby improving sexual,bone,metabolic and mental health.
基金This work was supported by the National Natural Science Foundation of China(Nos.30801003,30972683 and 30901310).
文摘Immunoglobulin superfamily(IgSF)members account for a large proportion of cell adhesion molecules that perform important immunological functions,including recognizing a variety of counterpart molecules on the cell surface or extracellular matrix.The findings that CD155/poliovirus receptor(PVR)and CD112/nectin-2 are the ligands for CD226/platelet and T-cell activation antigen 1(PTA1)/DNAX accessory molecular-1(DNAM-1),CD96/tactile and Washington University cell adhesion molecule(WUCAM)and that CD226 is physically and functionally associated with lymphocyte function-associated antigen-1(LFA-1)on natural killer(NK)and activated T cells have largely expanded our knowledge about the functions of CD226,CD96,WUCAM and LFA-1 and their respective ligands,CD155,CD112,intercellular adhesion molecule(ICAM)-1 and junctional adhesion molecule(JAM)-1.The interactions of these receptors and their ligands are involved in many key functions of immune cells including naive T cells,cytotoxic T cells,NK cells,NK T cells,monocytes,dendritic cells,mast cells and platelets/megakaryocytes.
基金This work was supported by the National Program for Key Basic Research Project(G1998051002)the National High Technology Research and Development Program(2001 AA221041+1 种基金2002BA711A01-03)the National Natural Science Foundation of China(Grant No.39830070).
文摘Proteins of the immunoglobulin superfamily (IgSF) are involved in a variety of spe- cific cell-cell interactions in the developing nervous system. To identify and characterize new members of this protein family in human nervous system, we screen the human fetal brain cDNA library and isolate a full-length cDNA clone which contains a 1032 bp open reading frame en- coding a protein of 344 amino acids. Sequence analysis reveals that it is a glycoprotein com- prised of three C2-1ike immunoglobulin domains and is anchored to the plasma membrane via a post-translationally attached glycosyl-phosphatidylinositol (GPI) moiety. The protein shows high sequence similarity to the rat Ntm (97%), so we term it human neurotrimin (NTM). Northern blot analysis reveals that (HUMAN)NTM has three different transcripts with the length of 3.2 kb, 4.0 kb and 9.0 kb respectively. It has a wider expression pattern than that of (RAT) Ntm. Notably, the expression of NTM in fetal brain is higher than that in mature brain and is stronger in nervous tumors than that in normal brain tissues. We insert an HA epitope tag between the third Ig-like domain of NTM and the site of GPI attachment, then construct it into the eukaryotic expression vector pcDNA3.1+/Zeocin. The pcDNA3.1-HA-NTM is transfected into the Chinese Hamster Ovary (CHO) cells. The results demonstrate that HA-NTM is expressed on the surface of CHO cells and could strengthen the aggregation of CHO-NTM cells.
