Diagnosis, treatment and genetic analysis of a child with infantile neuroaxonal dystrophy.

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disease characterized by early hypotonia, and rapid progression to psychomotor development regression, pyramidal tract positivity, and spastic quadriplegia. In this report, we describe a Chinese patient with INAD who presented with hypotonia, delayed motor and language development, and subsequently improved with rehabilitation training. Genetic testing revealed that the patient had compound heterozygous PLA2G6 gene variants, with the heterozygous c.496dupG (p.Glu166fsTer32) variant inherited from her father and the heterozygous c.2189T>G (p.Met730Arg) variant inherited from her mother. The p.Met730Arg was a novel variant. The protein structure predicts that the structural stability of the mutant protein may change, and the in vivo experimental results show that the expression of the mutant protein decrease. This study enriches the PLA2G6 gene mutation spectrum, and improves the clinicians' diagnostic awareness of INAD.

Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population.

The purpose of this study was to determine the genotype and allele frequencies of hMLH1 (-93G>A and I219V) and hMSH2 (-118T>C and IVS12-6T>C) polymorphisms in patients with gastric carcinoma and normal controls, and to evaluate the association between these polymorphisms and the risk of gastric cancer in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. A TaqMan assay was used to determine the genotype and allele frequencies of hMLH1 and hMSH2 polymorphisms in data obtained from 554 gastric cancer cases and 592 controls. Unconditional logistic regression was used to assess the association between the four single nucleotide polymorphisms (SNPs) and gastric carcinoma risk. No evidence of an association among any of the four polymorphisms and the risk of gastric cancer was observed. However, when gastric cancer patients were further stratified by age, gender, smoking status, alcohol use and clinicopathological characteristics, and compared with the control populations, the combined variant genotype hMSH2 -118T>C (TC+CC) was not only associated with an increased risk of gastric cancer in subgroups of younger subjects [ages ≤63years; adjusted odds ratio (OR)=1.51, 95% confidence interval (CI), 1.05-2.16], but also with diffuse tumors (adjusted OR=1.41, 95% CI, 1.01-1.96). These data indicate that the polymorphisms of -93G>A, I219V and IVS12-6T>C are not associated with the risk of gastric cancer. However, hMSH2-118T>C combined with variant genotypes (TC+CC) may confer a potential risk of gastric cancer in the Chinese population.

Genetic variations in the SMAD4 gene and gastric cancer susceptibility.

AIM: To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk. METHODS: Five tagging single nucleotide polymorphisms (tSNPs) in the SMAD4 gene were selected and genotyped in 322 gastric cancer cases and 351 cancer-free controls in a Chinese population by using the polymerase chain reaction restriction fragment length polymorphism method. Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to tumors. RESULTS: In the single-locus analysis, two significantly decreased risk polymorphisms for gastric cancer were observed: the SNP3 rs17663887 TC genotype (adjusted odds ratio = 0.38, 95% confidence interval: 0.21-0.71), compared with the wild-type TT genotype and the SNP5 rs12456284 GG genotype (0.31, 0.16-0.60), and with the wild-type AA genotype. In the combined analyses of these two tSNPs, the combined genotypes with 2-3 protective alleles (SNP3 C and SNP5 G allele) had a significantly decreased risk of gastric cancer (0.28, 0.16-0.49) than those with 0-1 protective allele. Furthermore, individuals with 0-1 protective allele had significantly decreased SMAD4 protein expression levels in the normal tissues adjacent to tumors than those with 2-3 protective alleles (P = 0.025). CONCLUSION: These results suggest that genetic variants in the SMAD4 gene play a protective role in gastric cancer in a Chinese population.

[Immunological killing effect of recombicant adenovirus vector rAD-mTERT-m4-1BBL on mouse hepatoma cell line Hepa1-6 cells co-cultured with T lymphocytes].

OBJECTIVE: To study the immunological suppressing effect of recombinant adenovirus vector rAD-mTERT promotor-m4-1BBL (rAD-mTERT) on mouse hepatoma cell line Hepa1-6 cells in co-culture with T lymphocytes. METHODS: Adding recombinant adenovirus rAD, rAD-CMV-m4-1BBL (rAD-CMV) and rAD-mTERT to Hepa1-6 and L929 cells, respectively, to observe the effect of these adenoviruses on growth and apoptosis of these cells in co-culture with T lymphocytes. RESULTS: Adding adenovirus significantly suppressed the growth and slightly increased apoptosis of the two types of cells (P < 0.05). rAD-mTERT promotor-m4-1BBL showed only pro-apoptotic effect on Hepa1-6 cells. When co-cultured with T lymphocytes, rAD-CMV-m4-1BBL showed promoting effect on apoptosis of the cells. Compared with that of T cells pre-co-culture, CD4(+) and CD8(+) T cells were proliferated, and the ratio of CD4/CD8 was significantly reduced (from 1.27 to 1.08). CONCLUSION: Adding the recombinant adenoviruses only suppresses the cell growth, but not promotes their apoptosis. In co-culture with T lymphocytes, recombinant adenovirus vector rAD-mTERT promotor-m4-1BBL can targetingly suppress the growth and induce apoptosis of Hepa1-6 cells. The apoptosis is induced through the immunological killing effect of T lymphocytes.

[Relationship among the XhaI and EcoRI locus polymorphisms of apolipoprotein B gene, serum lipid metabolism and gallstone disease].

OBJECTIVES: To explore the relationship between the XbaI and EcoRI locus polymorphisms of apolipoprotein B gene and gallstone disease. METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used to analyze the genotype of the ApoB gene in 106 patients and 105 controls, according to the design of case control study. RESULTS: The frequencies of X+X- and X-X- of XbaI locus polymorphism were significantly different between the patients and controls and the frequency of X+ allele in the patients was significantly higher than that in the controls (0.104 vs 0.052). Meanwhile, the levels of LDLc and ApoB in the patients were significantly higher than those in the controls among the group of X+X- genotype. The frequencies of E+E- and E+E+ of EcoRI locus polymorphism were significantly different between the patients and controls and the frequency of E-allele in the patients was significantly higher than that the in controls, and the level of LDLc with E+E- genotype was higher than that with E+E+ genotype among the patients. CONCLUSION: ApoB gene X+ allele of XbaI locus and E-allele of EcoRI locus may be the susceptible genes for gallstone disease, and variation of X+ and E-alleles may affect serum lipid metabolism and formation of gallstone.