A novel nonsense mutation in RHAG gene responsible for Rhnull phenotype in a Chinese individual.

BACKGROUND: Rhnull is a rare autosomal recessive phenotype, which is characterized by the lack of Rh antigen expression on the red blood cells (RBCs). Rhnull of the regulator type is caused by RHAG mutation. In this study, a novel nonsense mutation in RHAG gene was identified in a Chinese Rhnull individual. OBJECTIVES AND METHODS: Rh phenotypes of the Rhnull individual and his family members were typed by standard serological methods. DNA sequences of all ten exons of RHAG gene were analyzed using genomic DNA by polymerase chain reaction (PCR) and direct-sequencing. RESULTS: Serological testing results showed a D-C-c-E-e- phenotype in the proband. Molecular analyses revealed a 540C>A mutation in exon 4 of RHAG gene was present at the homozygous state in the proband. His parents were heterozygous for the mutation, and his brother didn't carry the mutation. The 540C>A mutation was nonsense mutation, which led to a premature stop codon (Tyr180stop). CONCLUSION: These results indicated that the 540C>A nonsense mutation in RHAG gene caused the regulator type of Rhnull phenotype in a Chinese individual. Our results contributed to a greater understanding of the genetic mechanisms of Rhnull phenotype.

Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.

A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and their structures were confirmed by single-crystal X-ray diffraction. Compared to some reported structures of 1,6-dihydro-1,2,4,5-tetrazine, these compounds can't be considered as having homoaromaticity. Their antiproliferative activities were evaluated against MCF-7, Bewo and HL-60 cells in vitro. Two compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 0.63-13.12µM. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 51 [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives with antiproliferative activity against MCF-7 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.716 and 0.723, respectively. Conventional r(2) values were 0.985 and 0.976, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives.

N'-[6-(3,5-Dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetra-zin-3-yl]butano-hydrazide.

In the title compound, C(11)H(16)N(8)O, the tetra-zine and pyrazole rings form a dihedral angle of 48.75 (2)°. In the crystal, N-H⋯O and N-H⋯N hydrogen bonds link the mol-ecules into layers parallel to (101).

N'-[6-(3,5-Dimethylpyrazol-1-yl)-1,2,4,5-tetrazin-3-yl]propanohydrazide.

In the title compound, C(10)H(14)N(8)O, the tetra-zine and pyrazole rings form a dihedral angle of 48.81 (2)°. In the crystal, inter-molecular N-H⋯N and N-H⋯O hydrogen bonds link the mol-ecules into layers parallel to (101).