PMS2 Pathogenic Variant in Lynch Syndrome-Associated Colorectal Cancer with Polyps.

Background Lynch syndrome (LS) is an autosomal dominant condition due to the germline mutation in the mismatch repair (MMR) genes including MLH1 , MSH2 , MSH6, and PMS2 (post-meiotic segregation increased 2). The MMR mutation carriers have high risk for cancers. Pathogenic PMS2 variants are rarely reported in LS-associated colorectal cancer (CRC) with colorectal polyps. The aim of the study was to investigate the genetic etiology of CRC in an individual with CRC with multiple colorectal polyps and a family history of cancers. Patients and Methods The index patient was an African male affected by CRC with multiple colorectal polyps. The clinical diagnostic for LS was based on the Amsterdam II criteria and pedigree. Next-generation sequencing with inherited cancer genes panel was used to detect the pathogenic variant. Results The patient fulfilled the Amsterdam II criteria and the pedigree revealed a family history of recurrent CRC. A deleterious PMS2 germline heterozygous mutation c.2192_2196delTAACT was detected. Conclusion Our study supports the notion that LS may be associated with polyps and shows the predisposition of PMS2 heterozygous mutation in LS-associated CRC at young age.

Enigma of the high prevalence of anti-SARS-CoV-2 antibodies in HIV-positive people with no symptoms of COVID-19 in Burkina Faso.

The severe acute respiratory syndrome due to the new coronavirus (SARS-CoV-2), responsible for coronavirus disease (COVID-19), has severely tested the global health response capacity, with predictions of a fatality for developing countries. To evaluate the prevalence of anti-SARS-CoV- 2 antibodies in People Living with HIV (PLHIV) with no COVID-19 symptoms in Burkina Faso. Seroprevalence was estimated by performing a qualitative screening test for SARS-CoV-2-specific immunoglobulins. The STANDARDTM Q COVID-19 IgM/IgG Combo Test kit from SD BIOSENSOR was used. Parameters like HIV plasma viral load, CD4 T cell count and C-Reactive Protein (CRP) expression were estimated. This study enrolled a total of 200 PLHIV aged 4-87 years who are asymptomatic for COVID-19. There were 36 (18%) positive for SARS-CoV-2 IgM and/or IgG of which three (1.50%) were positive for SARS-CoV-2 IgM and 33 (16.50%) for IgG. Among participants diagnosed as IgM positive, 66.67% (2/3) had the highest HIV viral loads with the lowest CD4 T cell counts (p<0.0001). The expression of CRP was relatively higher in COVID-19 IgG positive individuals (7.95±12.5 mg/L) than negative individuals (6.26±6.92 mg/L; p=0.37). The rate of IgG and IgM SARS-CoV-2 immunoglobulin carriage (18%), accompanied by a relatively high CRP levels, was revealed in this study among PLHIV. This serologic evidence and mild inflammation suggest that Burkina Faso escaped the worst, not necessarily because there were not many SARS-CoV-2 infections in its population, but because factors including genetic and environmental, might have resulted in many asymptomatic carriers.

Diabetes and COVID-19 in Congolese patients.

BACKGROUND: The global pandemic Coronavirus Disease 2019 (COVID-19) due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is reported to be potentially severe in patients with morbid conditions. One common reported comorbidities is diabetes. We aimed in this study to precise the clinical characteristics and outcomes in a series of congolese diabetic patients affected by COVID-19 infection. PATIENTS AND METHODS: We retrospectely studied from 256 COVID-19 patients, a cohort of 30 persons with previously known diabetes. The glycaemia controls have been obtained by plasma glucose assay. All patients have been tested positive to SARS-CoV-2 by RT-PCR method. RESULTS: The COVID-19 diabetic patients represented 11,7% of all COVID-19 patients with confidence interval of 95% [7,77-15,65]. Older individuals and male sex were predominent. Dyspnea and sauration of oxygen < 90 were significatives and added risk factors were noted in 63.3% of patients, particulary hyperglycaemia with hypertension or obesity. The mortality rate at the percentage of 36.7% was more prevalent in patients with added comorbidities (30%) versus without comorbidities (6.7%). CONCLUSION: Congolese COVID-19 diabetic patients of male sex and older age exhibiting arterial hypertension and obesity are the most exposed to severe COVID-19 and increasead mortality rate.

Truncus arteriosus communis: report of three cases and review of literature.

BACKGROUND: Truncus arteriosus communis (TAC) is a congenital heart defect in which the physiologic arterial common trunk was not divided into aorta and pulmonary artery trunk. OBJECTIVES: In this paper, we report on three observed cases from which we looked for (in conjunction with literature review) the different causes of TAC many of which have genetic origins. METHODS: We collected three clinical files of fetuses having a TAC. Two of them were examinated after a medical termination of pregnancy motivated by severe cardiopathy. The malformation had been diagnosed based on different techniques: echocardiography, skeletal radiography, arteriography, fetal autopsy, karyotype and fluorescence in situ hybridization (FISH). RESULTS: Imaging and fetopathological examination revealed the presence of TAC type 3 and 4 in the Van Praaghs classification. FISH analysis showed a 22q11.2 deletion in one fetus in favour of Digeorge syndrome. The karyotype analysis performed in two cases was normal. CONCLUSION: Truncus arteriosus is a rare pathology caused by numerous etiologies from which many of them have genetic origin. This malformation can be diagnosed early during prenatal period. Postmortem fetopathological examination allows a better diagnosis approach and eventually a genetic counseling in recurrent cases such as case of consanguinity.

The identification of Lynch syndrome in Congolese colorectal cancer patients.

BACKGROUND: We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. METHODS: We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). RESULTS: We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). CONCLUSION: The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo.

Altered p16 and Bcl-2 expression reflects pathologic development in hydatidiform moles and choriocarcinoma.

Abnormal trophoblast differentiation is the main cause of gestational trophoblast diseases in the case of hydatidiform moles and choriocarcinomas. Here we investigated the expression patterns of two gene products, p16 and Bcl-2, implicated in cell cycle regulation and apoptosis, respectively, using immunohistochemistry during normal placenta differentiation, hydatidiform moles (partial, complete and invasive) and post-molar choriocarcinomas. The p16 protein shows a gradual expression in cytotrophoblast of normal villous, from a p16 weak proliferative phenotype to a p16 strong invasive phenotype reaching a maximum around 17 weeks of gestation. The expression pattern in cytotrophoblast was similar in moles in contrast to the villous mesenchyme of invasive moles where p16 was strongly expressed. Bcl-2 expression was syncytiotrophoblast specific in normal placenta and moles and increased gradually during normal differentiation. The results explain the persistence of normal and molar villous fragments during their development and their dramatic invasion in the uterine arteries in case of invasive moles. In choriocarcinomas the weak Bcl-2 expression is associated with weak p16 expression indicating a great apoptotic and proliferative potentials. The results suggest that strong p16 expression in the villous mesenchyme may be responsible in part of the morbidity of the moles, and the key of cancer progression in the choriocarcinomas would be a fast cell-cycle turnover.

[Cytogenomic studies of hydatiform moles and gestational choriocarcinoma]. / Étude cytogénomique de la môle hydatiforme et du choriocarcinome gestationnel.

The complete hydatidiform mole (CHM), a gestational trophoblastic disease, is usually caused by the development of an androgenic egg whose genome is exclusively paternal. Due to parental imprinting, only trophoblasts develop in the absence of a fetus. CHM are diploid and no abnormal karyotype is observed. It is 46,XX in most cases and less frequently 46,XY. The major complication of this disease is gestational choriocarcinoma, a metastasizing tumor and a true allografted malignancy. This complication is infrequent in developed countries, but is more common in the developing countries and is then worsened by delayed care. The malignancies are often accompanied by acquired, possibly etiological genomic abnormalities. We investigated the presence of recurrent cytogenetic abnormalities in CHM and post-molar choriocarcinoma using metaphasic CGH (mCGH) and high-resolution 244K aCGH techniques. The 10 CHM studied by mCGH showed no chromosomal gains or losses. For post-molar choriocarcinoma, 11 tumors, whose diagnosis was verified by histopathology, were investigated by aCGH. Their androgenic nature and the absence of tumor DNA contamination by maternal DNA were verified by the analysis of microsatellite markers. Three choriocarcinoma cell lines (BeWo, JAR and JEG) were also analyzed by aCGH. The results allowed us to observe some chromosomal rearrangements in primary tumors, and more in the cell lines. Chromosomal abnormalities were confirmed by FISH and functional effect by immunohistochemical analysis of gene expression. Forty minimum critical regions (MCR) were defined on chromosomes. Candidate genes implicated in choriocarcinoma oncogenesis were selected. The presence in the MCR of many miRNA clusters whose expression is modulated by parental imprinting has been observed, for example in 14q32 or in 19q13.4. This suggests that, in gestational choriocarcinoma, the consequences of gene abnormalities directly linked to acquired chromosomal abnormalities are superimposed upon those of imprinted genes altered at fertilization.

Genome-wide high-resolution aCGH analysis of gestational choriocarcinomas.

Eleven samples of DNA from choriocarcinomas were studied by high resolution CGH-array 244 K. They were studied after histopathological confirmation of the diagnosis, of the androgenic etiology and after a microsatellite marker analysis confirming the absence of contamination of tumor DNA from maternal DNA. Three cell lines, BeWo, JAR, JEG were also studied by this high resolution pangenomic technique. According to aCGH analysis, the de novo choriocarcinomas exhibited simple chromosomal rearrangements or normal profiles. The cell lines showed various and complex chromosomal aberrations. 23 Minimal Critical Regions were defined that allowed us to list the genes that were potentially implicated. Among them, unusually high numbers of microRNA clusters and imprinted genes were observed.