👤 H Y Kroes

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for cardiovascular disease (CVD), but its characterization within the Japanese population remains unexplored. This systematic literature review synthesizes evidence on the association between Lp(a) levels and CVD in Japanese patients. To ensure comparability, the review focused on studies using the widely used LATEX-based immunoassay method. Most studies categorized patients into "high" and "low" Lp(a) groups; this review concentrates on findings from the "high" groups to evaluate the impact of elevated Lp(a). Although definitions of "high" Lp(a) varied, a consistent association between elevated Lp(a) and increased cardiovascular risk has been observed, aligning with international findings. Variability across studies was noted, likely due to differences in study design, endpoints, and follow-up durations. Although no approved therapies specifically target elevated Lp(a), several randomized controlled trials are currently ongoing. Continued research is essential to better understand the clinical implications of elevated Lp(a) among Japanese individuals. Show less

The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic (MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (P < .0001), which was significantly more methylated than those of the controls (P = .02). We have confirmed that this CpG island does function as a promoter in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance. Show less

We present two unrelated patients with various duplications in the caudal region. One patient presented with a duplication of the distal spine from L4, left double ureter, duplication of the vagina and cervix, and duplication of the distal colon. The second patient was diagnosed with a duplication of the colon, bladder, vagina and uterus. The first patient had an unaffected monozygotic twin sister. Dominguez et al. [1993: Am J Dis Child 147:1048-1052] presented six similar cases, and introduced the name "caudal duplication syndrome." The pathogenesis of the caudal duplication anomaly is unclear. The possibility of a polytopic primary developmental field defect or a disruptive sequence are discussed. On the other hand, somatic or germline mutations in certain developmental genes could be involved, as illustrated by the mouse mutations disorganisation and fused. DNA-analysis of the AXIN1 gene, the human homologue of the gene responsible for fused, performed in our first patient, did not show any apparent pathogenic mutation. Show less