Epidemiology of Spinal Muscular Atrophy Based on the Results of a Large-Scale Pilot Project on 202,908 Newborns.

Background: This study presents the findings of a newborn screening (NBS) pilot project for 5q-spinal muscular atrophy (5q-SMA) in multiple regions across Russia for during the year 2022. The aim was to assess the feasibility and reproducibility of NBS for SMA5q in diverse populations and estimate the real prevalence of 5q-SMA in Russia as well as the distribution of patients with different number of SMN2 copies.

Methods: The pilot project of NBS here was based on data, involving the analysis of 202,908 newborns.

Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the Gene.

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates.

Newborn Screening for Severe T and B Cell Lymphopenia Using TREC/KREC Detection: A Large-Scale Pilot Study of 202,908 Newborns.

Newborn screening (NBS) for severe inborn errors of immunity (IEI), affecting T lymphocytes, and implementing measurements of T cell receptor excision circles (TREC) has been shown to be effective in early diagnosis and improved prognosis of patients with these genetic disorders. Few studies conducted on smaller groups of newborns report results of NBS that also include measurement of kappa-deleting recombination excision circles (KREC) for IEI affecting B lymphocytes. A pilot NBS study utilizing TREC/KREC detection was conducted on 202,908 infants born in 8 regions of Russia over a 14-month period.

An Unusual Presentation of Novel Missense Variant in Gene: NM_000280.4:c.341A>G, p.(Asn114Ser).

This study investigates a unique and complex eye phenotype characterized by minimal iris defects, foveal hypoplasia, optic nerve coloboma, and severe posterior segment damage. Through genetic analysis and bioinformatic tools, a specific nonsynonymous substitution, p.(Asn114Ser), within the gene's paired domain is identified.

Complex Chromosomal Rearrangement Involving Chromosomes 10 and 11, Accompanied by Two Adjacent 11p14.1p13 and 11p13p12 Deletions, Identified in a Patient with WAGR Syndrome.

Three years ago, our patient, at that time a 16-month-old boy, was discovered to have bilateral kidney lesions with a giant tumor in the right kidney. Chemotherapy and bilateral nephron-sparing surgery (NSS) for Wilms tumor with nephroblastomatosis was carried out. The patient also had eye affection, including glaucoma, eye enlargement, megalocornea, severe corneal swelling and opacity, complete aniridia, and nystagmus.

Major Contribution of c.[1622T>C;3113C>T] Complex Allele and c.5882G>A Variant in -Related Retinal Dystrophy in an Eastern European Population.

Inherited retinal diseases (IRDs) constitute a prevalent group of inherited ocular disorders characterized by marked genetic diversity alongside moderate clinical variability. Among these, -related eye pathology stands as a prominent form affecting the retina. In this study, we conducted an in-depth analysis of 96 patients harboring variants in the European part of Russia.

Epidemiology of Gene Pathogenic Variants and Expected Prevalence of -Associated Congenital Aniridia across the Russian Federation: A Nationwide Study.

This study investigates the distribution of -associated congenital aniridia (AN) and WAGR syndrome across Russian Federation (RF) districts while characterizing gene variants. We contribute novel pathogenic variants and 11p13 chromosome region rearrangements to international databases based on a cohort of 379 AN patients (295 families, 295 probands) in Russia. We detail 100 newly characterized families (129 patients) recruited from clinical practice and specialized screening studies.

Co-Occurrence of Congenital Aniridia Due to Nonsense Variant p.(Cys94*) and Chromosome 21 Trisomy in the Same Patient.

This study aims to present a clinical case involving the unique co-occurrence of congenital aniridia and Down syndrome in a young girl and to analyze the combined impact of these conditions on the patient's phenotype. The investigation involved comprehensive pediatric and ophthalmological examinations alongside karyotyping and Sanger sequencing of the gene. The patient exhibited distinctive features associated with both congenital aniridia and Down syndrome, suggesting a potential exacerbation of their effects.

[Molecular genetics in diagnosis of Coats disease: combination of oligogenic variants associated with different forms of hereditary retinal dystrophy].

Coats disease (OMIM 300216) is a form of hereditary retinal dystrophy, which occurs due to congenital abnormality of retinal vessels and features unilateral exudative vitreoretinopathy. Coats disease mostly occurs sporadically; its genetic cause is still undetermined. Molecular genetic research including whole exome sequencing by the NGS method was used to define a genetic cause of the observed phenotype.

Genetic Heterogeneity of X-Linked Ichthyosis in the Republic of North Ossetia-Alania, Case Series Report.

North Caucasus has always been a residence of a lot of different authentic ethnic groups speaking different languages and still living their traditional lifestyle. The diversity appeared to be reflected in the accumulation of different mutations causing common inherited disorders. X-linked ichthyosis represents the second most common form of genodermatoses after ichthyosis vulgaris.

Corrigendum: Epidemiology of rare hereditary diseases in the European part of Russia: Point and cumulative prevalence.

[This corrects the article DOI: 10.3389/fgene.2021.

Relative Frequencies of Mutational Events in a Russian Cohort of Aniridia Patients in Comparison with the World's Population and the Human Genome.

Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome.

High frequency of complex CFTR alleles associated with c.1521_1523delCTT (F508del) in Russian cystic fibrosis patients.

Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun.

Epidemiology of Rare Hereditary Diseases in the European Part of Russia: Point and Cumulative Prevalence.

The issue of point prevalence, cumulative prevalence (CP), and burden of rare hereditary diseases (RHD), comprising 72-80% of the group of rare diseases, is discussed in many reports and is an urgent problem, which is associated with the rapid progress of genetic technology, the identification of thousands of genes, and the resulting problems in society. This work provides an epidemiological analysis of the groups of the most common RHDs (autosomal dominant, autosomal recessive, and X-linked) and their point prevalence (PP) and describes the structure of RHD diversity by medical areas in 14 spatially remote populations of the European part of Russia. The total size of the examined population is about 4 million.

Upstream ORF frameshift variants in the PAX6 5'UTR cause congenital aniridia.

Congenital aniridia (AN) is a severe autosomal dominant panocular disorder associated with pathogenic variants in the PAX6 gene. Previously, we performed a molecular genetic study of a large cohort of Russian patients with AN and revealed four noncoding nucleotide variants in the PAX6 5'UTR. 14 additional PAX6-5'UTR variants were also reported in the literature, but the mechanism of their pathogenicity remained unclear.

Genetic Variant c.245A>G (p.Asn82Ser) in Gene Is a Frequent Cause of Hereditary Nonsyndromic Sensorineural Hearing Loss in Chuvash Population.

Hereditary nonsyndromic sensorineural hearing loss is a disease in which hearing loss occurs due to damage to the organ of the inner ear, the auditory nerve, or the center in the brain that is responsible for the perception of sound, characterized by wide locus and allelic heterogeneity and different types of inheritance. Given the diversity of population of the Russian Federation, it seems necessary to study the ethnic characteristics of the molecular causes of the disease. The aim is to study the molecular and genetic causes of hereditary sensorineural hearing loss in Chuvash, the fifth largest ethnic group in Russia.

A novel mutation in the gene in a family from Dagestan with members affected by Zellweger spectrum disorder.

Background: Peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders that affect multiple organ systems. Approximately 80% of PBD patients are classifiedin the Zellweger syndrome spectrum, which is generally caused by mutations in the , or genes.

Methods: We present the clinical characteristics of three male members with cholestatic hepatopathy and developmental delay.

Mutation in PHACTR1 associated with multifocal epilepsy with infantile spasms and hypsarrhythmia.

A young boy with multifocal epilepsy with infantile spasms and hypsarrhythmia with minimal organic lesions of brain structures underwent DNA diagnosis using whole-exome sequencing. A heterozygous amino-acid substitution p.L519R in a PHACTR1 gene was identified.

Prenatal diagnosis of Norrie disease after whole exome sequencing of an affected proband during an ongoing pregnancy: a case report.

Background: Hereditary ophthalmic pathology is a genetically heterogeneous group of diseases that occur either as an isolated eye disorder or as a symptom of hereditary syndromes (chromosomal or monogenic). Thus, a diagnostic search in some cases of ophthalmic pathology can be time- and cost-consuming. The most challenging situation can arise when prenatal diagnosis is needed during an ongoing pregnancy.

Clinical Presentation of the c.3844T>C (p.Trp1282Arg, W1282R) Variant in Russian Cystic Fibrosis Patients.

The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation.

A sporadic case of congenital aniridia caused by pericentric inversion inv(11)(p13q14) associated with a 977 kb deletion in the 11p13 region.

Background: Because of the significant occurrence of "WAGR-region" deletions among de novo mutations detected in congenital aniridia, DNA diagnosis is critical for all sporadic cases of aniridia due to its help in making an early diagnosis of WAGR syndrome. Standard cytogenetic karyotype study is a necessary step of molecular diagnostics in patients with deletions and in the patients' parents as it reveals complex chromosomal rearrangements and the risk of having another affected child, as well as to provide prenatal and/or preimplantation diagnostics.

Case Presentation: DNA samples were obtained from the proband (a 2-year-old boy) and his two healthy parents.

[Presentation of a rare case of hereditary hearing loss with X-linked recessive inheritance associated with the POU3F4 gene].

Congenital hearing loss is one of the most frequent inherited human pathologies, occurring in 1-2 out of 1000 newborns. X-linked hearing loss occurs in 1-5% of all congenital hearing impairments. The proband (a man) and his affected brother have profound prelingual non-syndromic neurosensory hearing loss.