Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis.

N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73-1.19) were found; however, the results showed significant heterogeneity (I2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes. In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations.

A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.

The purpose of this study was to identify the clinical features and mutations in the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations were included in the study. All members underwent complete ophthalmic examination. Molecular genetic analysis was performed on all subjects. All exons of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences were compared with a reference database. Variations were evaluated in family members as well as 100 normal controls. Changes in structure and function of the protein induced by amino acid variation were predicted by bioinformatic analysis. Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present in all patients diagnosed with MFS. The novel heterozygous missense mutation c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not in other family members or 100 normal controls. This mutation caused an amino acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1 protein. This mutation occurred in a highly conserved region and may cause structural and functional changes in the protein according to our bioinformatic analysis. Our results suggest that the novel mutation C781W of FBN1 is responsible for the pathogenesis of MFS in this pedigree.

A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.

Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.

A novel NF1 frame-shift mutation (c.702_703delGT) in a Chinese family with neurofibromatosis type 1.

This study aimed to characterize the clinical features of a Chinese pedigree with neurofibromatosis type 1 (NF1) and to identify mutations in the NF1 gene. In this three-generation family containing 8 members, 5 had been diagnosed with NF1 and the others were asymptomatic. All members of the family underwent complete medical examinations. Molecular genetic analyses were performed on all subjects included in the study. All exons of NF1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database. Possible changes in function of the protein induced by amino acid variants were predicted by bioinformatic analysis. In this family, the 5 patients presented different clinical phenotypes, but all manifested typical café-au-lait macules. One novel frame-shift mutation, c.702_703delGT, in exon 7 of NF1 was identified in all affected family members, but not in the unaffected family members or in 102 normal controls. This mutation generates a premature stop codon at amino acid position 720. Additionally, a synonymous mutation c.702 G>A was found in 3 family members, including 2 affected and 1 normal individuals. In conclusion, our study suggests that a novel c.702_703delGT frame-shift mutation in NF1 is likely to be responsible for the pathogenesis of NF1 in this family. To the best of our knowledge, it is the first time that a c.702_703delGT mutation has been identified in a family with neurofibromatosis type 1.

Confirmation of a purple-leaved plum graft hybrid.

Fifty-seven scions from an adult purple-leaved plum tree were grafted onto the crown of a 6-year-old Yuhuang plum tree and compared to the control of a non-grafted tree. The floral buds of the purple-leaved plum were fully removed before blossoming to avoid sexual hybridization between the two species. The seeds of the Yuhuang plum were picked in July and sown in the spring after stratification. Three, eleven and eight variants with purplish red leaves were found among the seedlings that grew from the seeds picked in 1999, 2000, and 2001, respectively. The ratio of variant occurrence ranged from 2.3 to 15.8%. Our results confirmed the observation of a graft hybrid by Luther Burbank.