No association between transmembrane protein-tyrosine phosphatase receptor type C (PTPRC) exon A 77C>G transversion and liver transplant rejection

This study was carried out to evaluate the association between 77C>G transversion (rs17612648) in exon A of the PTPRC gene and liver transplant rejection. No significant differences in genotype and allele frequencies of the 77C>G transversion were detected between recipients without rejection (n = 106) and recipients with rejection (n = 104). In conclusion, there was no evidence for the contribution of the 77C>G transversion in susceptibility to liver transplant rejection in a Caucasian population.     

A transmembrane protein-tyrosine phosphatase receptor type C (CD45) exon A point mutation (77 C to G) is not associated with the development of type 1 diabetes mellitus in a German population.

To investigate whether a C to G transversion at position 77 in exon A of the CD45 gene is associated with the development of diabetes mellitus type 1 (T1D), we studied 165 patients and 220 control individuals. The frequency of the 77G allele in the control group was 1.1%, which was not significantly different from the 1.2% found in the patient group (P = 0.922). The C to G transversion does not seem to be associated with susceptibility for T1D.     

A transmembrane protein–tyrosine phosphatase receptor type C (CD45) exon A point mutation (77 C to G) is not associated with the development of type 1 diabetes mellitus in a German population

To investigate whether a C to G transversion at position 77 in exon A of the CD45 gene is associated with the development of diabetes mellitus type 1 (T1D), we studied 165 patients and 220 control individuals. The frequency of the 77G allele in the control group was 1.1%, which was not significantly different from the 1.2% found in the patient group (P = 0.922). The C to G transversion does not seem to be associated with susceptibility for T1D.     

No association of the CD45 77C>G transversion with inflammatory bowel disease in German patients

A 77C>G transversion in exon A of the CD45 gene was investigated in patients with inflammatory bowel disease (IBD) and controls. The distribution of the 77G allele was not significantly different between patients and controls. We found no evidence for the contribution of the 77C>G transversion in susceptibility to IBD.     

Enhanced frequency of a PTPRC (CD45) exon A mutation (77C-->G) in systemic sclerosis

A point mutation in exon A (C to G transversion at position 77) of human PTPRC (CD45) has recently been associated with the development of multiple sclerosis (MS) for at least a subgroup of patients. In the present report, we studied the frequency of the 77C-->G transversion in two other autoimmune diseases namely systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The mutation was found with significantly enhanced frequency in patients suffering from SSc suggesting that PTPRC could play a role as susceptibility gene not only in MS but also in other autoimmune diseases. Further understanding of the mode of interaction of mutant PTPRC with other susceptibility genes may uncover mechanisms common in various autoimmune disorders.     

77 C/G mutation in the tyrosine phosphatase CD45 gene and autoimmune hepatitis: evidence for a genetic link

Autoimmune hepatitis is a chronic immune-mediated disease characterized by a loss of tolerance against liver resident antigens. The genetic background of autoimmune hepatitis is considered to be polygenic. Here we analyzed the genetic association of the tyrosine phosphatase CD45 and autoimmune hepatitis. CD45 plays an important role in normal antigen receptor mediated signaling in T and B cells. A point mutation at nucleotide position 77 of the CD45 gene results in abnormal CD45 splicing. In this study a significantly higher frequency of the 77 C/G genotype was observed in 190 autoimmune hepatitis patients when compared to 210 healthy blood donors. Our data identify CD45 as a gene associated with AIH, and further substantiates the hypothesis that CD45 represents a modifier gene of human autoimmunity.     

CD45 exon 4 point mutation does not confer susceptibility to type 1 diabetes mellitus or Graves’ disease

A point mutation in the leukocyte common antigen (CD45, C → G77, exon 4) was investigated in patients with type 1 diabetes (IDDM), patients with Graves’ disease and controls. The distribution did not differ significantly between patients and controls. This CD45 variant does not therefore confer susceptibility to either IDDM or Graves’ disease.     

A novel mitochondrial DNA tRNAIle (m.4322dupC) mutation associated with idiopathic dilated cardiomyopathy.

We identified a novel heteroplasmic mitochondrial DNA (mtDNA) (m.4322dupC) mutation in tRNA gene associated with isolated dilated cardiomyopathy (DCM) as maternal trait. Mutation screening techniques and automated DNA sequencing were performed to identify mtDNA mutations and to assess heteroplasmy in family's proband and healthy control subjects. All family members tested had heteroplasmic mtDNA m.4322dupC mutation. We also screened 350 normal controls for this mutation and found no evidence of heteroplasmy. The m.4322dupC mutation was found in the skeletal tissue from the proband that exhibited slightly reduced deficiency of mitochondrial respiratory chain enzymes (complex III). The present study reports the novel m.4322dupC mutation in tRNA gene, which is possibly associated to the disease, to isolated DCM. It was localized in a hot-spot region for mutations and is possibly pathogenic because of a cosegregation with the matrilineal transmission of DCM.     

Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G)

Mutation of mitochondria) (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS. © 1994 Wiley-Liss, Inc.     

No association between a promoter dopamine D(4) receptor gene variant and schizophrenia

The dopamine D(4) receptor has been implicated in the pathogenesis of schizophrenia. An association between a putative functional promoter polymorphism (-521C/T) in the dopamine D(4) receptor gene (DRD4) and schizophrenia was recently reported. In the present study, patients with schizophrenia (n = 132) and control subjects (n = 388) were analyzed with respect to the DRD4 - 521C/T polymorphism. No significant case control differences emerged. The present results do not support a major role for DRD4 in the etiology of schizophrenia among Caucasians from Sweden.     

CD45-associated protein promotes the response of primary CD4 T cells to low-potency T-cell receptor (TCR) stimulation and facilitates CD45 association with CD3/TCR and lck

Although it is clear that the CD45 tyrosine phosphatase is required for efficient T-cell activation and T-cell development, the factors that regulate CD45 function remain uncertain. Previous data have indicated that there is an association of CD45 with CD4 and the T-cell receptor (TCR) complex controlled by the variable ectodomain of CD45 and, following activation, by high- and low-potency peptides. This suggests that controlling substrate access to CD45 may be an important regulatory mechanism during T-cell activation. In the present study we have examined the role of the transmembrane adapter-like molecule CD45-associated protein (CD45-AP) in regulating the association of CD45 with CD3/TCR and lck, and in regulating primary CD4(+) T-lymphocyte activation. In CD4(+) T cells from CD45-AP-deficient mice, coimmunoprecipitation of CD45 with the CD3/TCR complex, in addition to lck, is significantly reduced compared with wild-type T cells. Functionally, this correlates with a decreased proliferative response, a decrease in interleukin (IL)-2 production, and a decrease in calcium flux upon stimulation with a low-potency altered peptide ligand. However, the response of CD45-AP-deficient T cells to stimulation with a high-avidity agonist peptide was largely intact, except for a modest decrease in IL-2 production. These data suggest that CD45-AP promotes or stabilizes the association of CD45 with substrates and regulates the threshold of T-cell activation.     

A double mutation (G11778A and G12192A) in mitochondrial DNA associated with Leber's hereditary optic neuropathy and cardiomyopathy

 We report a male patient with Leber's hereditary optic neuropathy (LHON) and hypertrophic cardiomyopathy. Besides a G11778A mutation in the ND4 gene of the mitochondrial DNA (mtDNA), one of the most common mutations in LHON patients, sequencing of total mtDNA revealed a G12192A mutation in the tRNA (His) gene that was recently noted to be a risk factor for cardiomyopathy. Because no case of LHON presenting with cardiomyopathy has been reported, the present finding suggests that the G12192A mutation caused cardiomyopathy as an additional symptom. In the present case, the double pathogenic mtDNA mutations may be associated either synergistically or concomitantly with two different clinical manifestations. Received: July 4, 2002 / Accepted: October 28, 2002 Acknowledgments We thank Mayuko Kato, Yoko Murase, and Munemitsu Yuasa for technical assistance. This work was supported in part by a Research Grant (13B-1) for Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare of Japan (Y.G.). Correspondence to:Y. Goto     

HBV感染孕妇体内病毒前C区G1896A变异与母婴垂直传播的关系

目的 分析孕妇体内乙型肝炎病毒(HBV)前C区G1896A变异对母婴垂直传播的影响.方法 收集40例本院妇产科HBeAg(-)/HBsAg( )的孕妇血标本,同时收集这些孕妇分娩时新生儿脐带血40例.荧光定量PCR(FQ-PCR)检测HBV孕妇血清和新生儿脐带血中HBV-DNA栽量,PCR-ELISA法检测孕妇血清中HBV-DNA前C区G1896A变异.分析HBV前C区G1896A变异及孕妇血清HBV-DNA载量对母婴垂直传播率的影响.结果 40例孕妇血清共检测到25例HBV前C区G1896A变异(62.5%);变异组母婴垂直传播发生率为44.0%(11/25),未变异组母婴垂直传播发生率为40.0%(6/15),二组比较无统计学差异(x2=0.0614,P＞0.05).孕妇血中HBV-DNA高载量组(≥1×105 copies/ml)母婴垂直传播发生率为62.5%(10/16),低栽量组(＜1 × 105 copies/ml)母婴垂直传播发生率为29.2%(7/24),二组相比有显著性差异(x2=4.3649,P＜0.05).结论 HBV前C区G1896A变异未增加母婴HBV垂直传播率,孕妇血清中HBV-DNA栽量升高是母婴HBV垂直传播危险因素.