WES-based screening of 7,000 newborns: A pilot study in Russia.

The effective implementation of whole-exome sequencing- and whole-genome sequencing-based diagnostics in the management of children affected with genetic diseases and the rapid decrease in the cost of next-generation sequencing (NGS) enables the expansion of this method to newborn genetic screening programs. Such NGS-based screening greatly increases the number of diseases that can be detected compared to conventional newborn screening, as the latter is aimed at early detection of a limited number of inborn diseases. Moreover, genetic testing provides new possibilities for family members of the proband, as many variants responsible for adult-onset conditions are inherited from the parents.

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.

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.

Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus.

Background: Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others.

Case Presentation: NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found.

Molecular diagnosis of tuberous sclerosis complex in fetuses and infants: an institutional case series.

Objective: We describe the clinical and genetic characteristics of fetuses and infants diagnosed with tuberous sclerosis complex (TSC) in our centre, prenatally or neonatally, for a better understanding of the benefits of early screening.

Methods: In this retrospective study, we analysed the data on one fetus and nine infants with a definitive TSC diagnosis by genetic criteria (five patients carrying variants and 5 patients carrying variants). We explored the differences between phenotypes of patients carrying and pathogenic variants.

CAMK2D De Novo Missense Variant in Patient with Syndromic Neurodevelopmental Disorder: A Case Report.

Background: Intellectual disability with developmental delay is the most common developmental disorder. However, this diagnosis is rarely associated with congenital cardiomyopathy. In the current report, we present the case of a patient suffering from dilated cardiomyopathy and developmental delay.

De Novo Variant in the Gene as a Possible Cause of Neonatal Seizures.

Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749).

Familial Predisposition to Leiomyomata: Searching for Protective Genetic Factors.

In order to determine genetic loci associated with decreasing risk of uterine leiomyomata (UL), a genome-wide association study (GWAS) was performed. We analyzed a group of patients with a family history of UL and a control group consisting of patients without uterine fibroids and a family predisposition to this pathology. Six significant single nucleotide polymorphisms were selected for PCR-genotyping of a large data set of patients with UL.

Prenatal diagnosis of Prader-Willi syndrome due to uniparental disomy with NIPS: Case report and literature review.

Background: PWS is challenging to diagnose prenatally due to a lack of precise and well-characterized fetal phenotypes and noninvasive markers. Here we present the case of prenatal diagnosis of Prader-Willi syndrome, which was suspected with whole-genome NIPS.

Methods: Whole-genome noninvasive prenatal screening showed a high risk for trisomy 15.

In silico size selection is effective in reducing false positive NIPS cases of monosomy X that are due to maternal mosaic monosomy X.

Objectives: The aim of this study was to establish maternal contribution to false positive noninvasive prenatal DNA screening (NIPS) results and develop the method to distinguish maternal and fetal origin of high-risk monosomy X NIPS calls including mosaic maternal cases.

Method: A total of 906 women carrying singleton pregnancies have been recruited. Maternal plasma DNA semiconductor massive parallel sequencing was performed to detect common aneuploidies.