Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies.

BACKGROUND: Whole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients. RESULTS: Here we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients. CONCLUSIONS: Therefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.

De novo start-loss variant in HIRA in patient with DiGeorge-like syndrome.

A case of a newborn with tetralogy of Fallot, corpus callosum hypoplasia, and phenotypic features similar to DiGeorge syndrome. Chromosomal microarray analysis did not reveal any alterations. Whole exome sequencing and Sanger sequencing identified a de novo variant in the HIRA gene resulting in the loss of the start codon.

Does the uterine microbiota affect the reproductive outcomes in women with recurrent implantation failures?

BACKGROUND: Inefficiency of in vitro fertilization (IVF) programs can be caused by implantation failures. The uterine microbiota can influence the implantation process. However, it still remains unclear whether opportunistic microorganisms detected in the endometrium have a negative impact on the implantation success. The aim of our study was to evaluate the influence of the uterine microbiota on the embryo implantation success in patients undergoing assisted reproductive technologies. METHODS: The study included 130 women diagnosed with infertility. The patients were divided into three groups: group I included women with the first IVF attempt (n = 39); group II included patients with recurrent implantation failure following embryo transfer with ovarian stimulation (n = 27); group III consisted of women with recurrent implantation failure following frozen-thawed embryo transfer (n = 64). We performed microbiological examination of the embryo transfer catheter which was removed from the uterine cavity after embryo transfer; cervical discharge of all the patients was studied as well. Thirty patients were selected for metagenomic sequencing. RESULTS: The study showed that the uterine cavity is not free of microorganisms. A total of 44 species of microorganisms were detected: 26 species of opportunistic organisms and 18 species of commensals (14 species of lactobacilli and 4 species of bifidobacteria). Obligate anaerobic microorganisms and Gardnerella vaginalis were detected more frequently in group I compared to group III (strict anaerobes-15.4 and 1.6%; G. vaginalis-12.8 and 1.6%, respectively) (p < 0.05). However, this fact did not have a negative influence on the pregnancy rate: it was 51.3% in group I, it was 29.6% and 35.9% in women with recurrent implantation failures, respectively. CONCLUSION: Opportunistic microorganisms which were revealed in low or moderate titers (103-105 CFU/ml) in the uterine cavity and cervical canal did not affect the pregnancy rate in the women in the study groups. The microflora of the uterine cavity and cervical canal differed in qualitative composition in 87.9% of patients, therefore, we can suggest that the uterine cavity may form its own microbiota. The microbiota of the uterine cavity is characterized by fewer species diversity compared to the microbiota of the cervical canal.