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.

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.

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.

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.

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.

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.

Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis.

Background: Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract-microcornea syndromes.

Results: In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocular malformation. Both cases manifested bilateral microphthalmia and severe anterior segment dysgenesis, primarily characterized by congenital aphakia, microcornea, and iris hypoplasia/aniridia.

Preferentially Paternal Origin of De Novo 11p13 Chromosome Deletions Revealed in Patients with Congenital Aniridia and WAGR Syndrome.

The frequency of pathogenic large chromosome rearrangements detected in patients with different Mendelian diseases is truly diverse and can be remarkably high. Chromosome breaks could arise through different known mechanisms. Congenital -associated aniridia is a hereditary eye disorder caused by mutations or chromosome rearrangements involving the gene.

Analysis of genotype-phenotype correlations in -associated aniridia.

BackgroundAniridia is a severe autosomal dominant panocular disorder associated with pathogenic sequence variants of the gene or 11p13 chromosomal aberrations encompassing the coding and/or regulatory regions of the gene in a heterozygous state. Patients with aniridia display several ocular anomalies including foveal hypoplasia, cataract, keratopathy, and glaucoma, which can vary in severity and combination.MethodsA cohort of 155 patients from 125 unrelated families with identified point pathogenic variants (118 patients) or large chromosomal 11p13 deletions (37 patients) was analyzed.

Epidemiology of Hereditary Diseases in the Karachay-Cherkess Republic.

Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in different modern open populations is important.

LMO2 gene deletions significantly worsen the prognosis of Wilms' tumor development in patients with WAGR syndrome.

WAGR syndrome (OMIM #194072) is a rare genetic disorder that consists of development of Wilms' tumor (nephroblastoma), aniridia, genitourinary anomalies and intellectual disability (mental retardation). It is associated with WAGR-region deletions in the 11p13 chromosome region. Our previous study of congenital aniridia patients revealed a noticeable number of aniridia patients with WAGR-region deletions but without Wilms' tumor in their medical history.

Study of the genetic load and diversity of hereditary diseases in the Russian population of the Karachay-Cherkess Republic.

The genetic load and diversity of monogenic hereditary diseases (HD) in the Russian population of Karachay-Cherkess Republic (KCHR), living in 10 administrative and municipal divisions, were studied. The total size of the population surveyed was 410,367 people, including 134,756 Russians. In total, 385 patients from 281 families were registered among Russians of KCHR.

Primary microcephaly case from the Karachay-Cherkess Republic poses an additional support for microcephaly and Seckel syndrome spectrum disorders.

Background: Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel syndrome.

Case Presentation: Clinical exome sequencing of the proband revealed a novel homozygous single nucleotide deletion in ASPM gene, c.

Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles.

Hypotrichosis is an abnormal condition characterized by decreased hair density and various defects in hair structure and growth patterns. In particular, in woolly hair, hypotrichosis is characterized by a tightly curled structure and abnormal growth. In this study, we present a detailed comparative examination of individuals affected by autosomal-recessive hypotrichosis (ARH), which distinguishes two types of ARH.