Novel variants of CYP21A2 in Vietnamese patients with congenital adrenal hyperplasia.

BACKGROUND: Congenital adrenal hyperplasia (CAH) (OMIM #201910) is a complex disease most often caused by pathogenic variant of the CYP21A2 gene. We have designed an efficient multistep approach to diagnose and classify CAH cases due to CYP21A2 variant and to study the genotype-phenotype relationship. METHODS: A large cohort of 212 Vietnamese patients from 204 families was recruited. We utilized Multiplex Ligation-dependent Probe Amplification to identify large deletion or rearrangement followed by complete gene sequencing of CYP21A2 to map single-nucleotide changes and possible novel variants. RESULTS: Pathogenic variants were identified in 398 out of 408 alleles (97.5%). The variants indexed span across most of the CYP21A2 gene regions. The most common genotypes were: I2g/I2g (15.35%); Del/Del (14.4%); Del/I2g (10.89%); p.R356W/p.R356W (6.44%); and exon 1-3 del/exon 1-3 del (5.44%). In addition to the previously characterized and documented variants, we also discovered six novel variants which were not previously reported, in silico tools were used to support the pathogenicity of these variants. CONCLUSION: The result will contribute in further understanding the genotype-phenotype relationship of CAH patients and to guide better treatment and management of the affected.

[External phased-array MR imaging preoperative assessment of rectal cancer]. / Bilan pré opératoire des cancers du rectum en IRM pelvienne haute résolution avec antenne en réseau phasé.

The main problem associated with rectal cancer treatment is tumor recurrence. Randomized controlled studies have shown that adjuvant preoperative radiation therapy is effective for reducing local recurrence. These studies have also demonstrated that there are groups of rectal cancer patients with differing degrees of risk for local recurrence. At one end of the spectrum is the low-risk group: patients with superficial rectal cancer, who can be treated with surgery alone. At the other end is the high-risk group: patients with a close or involved resection margin at total mesorectal excision, the very advanced tumors that require a longer course of chemotherapy and radiation therapy, and extensive surgery. Paramount for this selection and differentiated treatment is a reliable preoperative test that can be used to distinguish these groups of patients. In this review article, we will discuss the role of high-resolution phased array MRI among the other imaging modalities such as endorectal MRI, endorectal US, and CT. We will also discuss and illustrate MR imaging results in terms of T stage, circumferential resection margin, locally advanced rectal cancer, and N stage.

Interdomain linkers of homologous response regulators determine their mechanism of action.

OmpR and PhoB are response regulators that contain an N-terminal phosphorylation domain and a C-terminal DNA binding effector domain connected by a flexible interdomain linker. Phosphorylation of the N terminus results in an increase in affinity for specific DNA and the subsequent regulation of gene expression. Despite their sequence and structural similarity, OmpR and PhoB employ different mechanisms to regulate their effector domains. Phosphorylation of OmpR in the N terminus stimulates the DNA binding affinity of the C terminus, whereas phosphorylation of the PhoB N terminus relieves inhibition of the C terminus, enabling it to bind to DNA. Chimeras between OmpR and PhoB containing either interdomain linker were constructed to explore the basis of the differences in their activation mechanisms. Our results indicate that effector domain regulation by either N terminus requires its cognate interdomain linker. In addition, our findings suggest that the isolated C terminus of OmpR is not sufficient for a productive interaction with RNA polymerase.