Inferring bona fide Differentially Expressed Genes and Their Variants Associated with Vitamin K Deficiency Using a Systems Genetics Approach.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied disease conditions. In this work, we ascertained the differentially expressed genes (DEGs) and variants associated with individual subpopulations of VK disease phenotypes, viz., myocardial infarction, renal failure and prostate cancer. We sought to ask whether or not any DEGs harbor pathogenic variants common in these conditions, attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Is Pouch Specific to Colon and Not Ileum?

BACKGROUND: Congenital Pouch Colon (CPC) is an anorectal anomaly with an incidence of 3.5:1 in males and females, respectively. We have earlier reported CPC to be quite prevalent in north Indian tertiary care centers. OBJECTIVE: In this article, we deliberate on the possible causes associated with CPC bringing the manifestation of the disease. In addition, we throw insights on the effective role of this congenital anomaly in Colon and provide systems genomic evaluation by comparing our recent analysis to that of Colon and Ileum based on Next-Generation Sequencing (NGS) studies. CONCLUSION: In this commentary article, we argue that a host of epigenetic factors could be the reason why the disease is manifested in colon alone. We further hypothesize on the few unmet challenges linking epigenetics to understand the genetic variants.

Congenital Pouch Colon: Role of Genetics or Environmental Influence?

BACKGROUND: Congenital pouch colon (CPC), a high type of anorectal malformation, is a sporadic disease and several environmental factors are known to be involved in its pathology. To the best of our knowledge, no familial incidence of CPC has been reported anywhere in the literature so far. AIM: In the present study, which is first of its kind, we have reported the familial incidences of CPC and also tried to elucidate the role of genetics in this pathology. METHODS: We have reported 1 familial pedigree of CPC and 2 incidences of dizygotic twins (DZ), out of them one is affected and another one is normal. Highly comprehensive microarray CytoScan HD from Affymetrix was employed to understand the defects underlying submicroscopic genomic imbalance like segment duplication and deletion of the twin patients vis-à-vis their parents and unaffected siblings in these DZ twins. RESULTS: A total of 21 copy number variations (CNVs) were reported in the patient samples that did not overlap with the CNVs in normal parents and healthy sibling, including 5 loss, 3 LOH and 13 gain with size varied from 95 bp to 77 kbp. Genetic analysis revealed involvement of 12 potential genetic loci on Chr 1, 2, 3, 4, 6, 11, and 16. CONCLUSION: Genetic study found that CPC could be a developmental disorder. These findings are important for further elucidating genetic causes of CPC pathogenesis.

Role of plain abdominal radiographs in predicting type of congenital pouch colon.

BACKGROUND: Congenital pouch colon (CPC) is a rare form of high ano-rectal malformation (ARM) in which part of or the entire colon is replaced by a pouch with a fistula to the genito-urinary tract. According to the Saxena-Mathur classification CPC is divided into five types. Although plain abdominal radiographs are taken in infants with suspicion of CPC to detect large dilatation of the pouch, the determination of the type of CPC is made during surgical exploration. Since large variations in the length of normal colon are present in the various types, management strategy options can be determined only at the time of surgery. OBJECTIVE: The aim of this study was to review abdominal radiographs of children with congenital pouch colon (CPC) and evaluate their value in determining the type of CPC prior to surgical exploration to assist pre-operative planning. MATERIALS AND METHODS: Over a 12-year period (1995-2007), CPC was documented in 80 children (52 boys and 28 girls, age range 1 day-9 years, median 2.4 days) and retrospective analysis of plain abdominal radiographs of 77 children at the time of presentation was performed. Radiographic findings were correlated with surgical findings. RESULTS: Of 77 children, 5 were excluded from the study since the pouch colon was perforated. The direction of the pouch apex was correlated with surgical findings to determine the CPC type (P<0.0001, Fisher exact test). Type 1 (17/18) and type 2 CPC (18/18) were characterized by a single large pouch with the apex positioned in the left hypochondrium. In type 3 CPC (2/2) the pouch apex was directed towards the right hypochondrium. In type 4 CPC the apex of the pouch was directed towards the right hypochondrium (28/33); however in 5 children it was towards the left hypochondrium. In type 5 CPC (n=1) the radiograph was inconclusive. CONCLUSION: Plain abdominal radiographs have a predictive value in determining the type of CPC and obviating the need for an invertogram.

Management of congenital pouch colon based on the Saxena-Mathur classification.

BACKGROUND: Management guidelines with regard to congenital pouch colon (CPC) are not clearly defined with regard to the type of pouch present. The aim of this study was to outline the management strategy and surgical approach to CPC using the Saxena-Mathur classification based on anatomical morphology of the pouch. METHODS: During a 12-year period (1995-2007), 426 patients were surgically managed for anorectal malformations at the RNT Medical College, Udaipur. Congenital pouch colon was documented in 80 patients and categorized into 5 types according the anatomical morphology. The management strategy depended upon the location of the pouch and its condition at the time of the surgery. RESULTS: In type 1 and type 2 CPC, a 1-stage (pouch excision and pull-through) or 3-stage procedure (ileostomy, pouch-coloplasty with pull-through, and ileostomy closure) was performed depending on the condition of the pouch (ischemic or healthy). In type 3 and type 4 CPC, a 3-stage procedure (pouch excision with colostomy, pull-through, and colostomy closure) was performed in all patients. In type 5 CPC, a 3-stage procedure (distal pouch excision with proximal pouch-coloplasty with ileostomy, pull-through, and colostomy closure) was successful. CONCLUSION: Management of CPC patients according the Saxena-Mathur classification provides a well-defined algorithm in the surgical approach according to the anatomical morphology of the pouch.

Congenital pouch colon with duplicate bladder exstrophy.

Congenital pouch colon, an unusual high anorectal malformation, is rarely associated with exstrophy variants. We describe a case of congenital pouch colon associated with duplicate bladder exstrophy, never reported before in literature. The relevant literature is reviewed, and the possible embryogenesis of this complex anomaly is suggested.