Cases report: Mosaic structural variants of the gene in previously genetically unconfirmed multiple osteochondromas.

Multiple osteochondromas (MO) is a rare autosomal dominant skeletal disorder characterized by the development of multiple benign tumors known as osteochondromas. The condition is predominantly caused by loss-of-function variants in the or genes, facilitating relatively precise clinical diagnosis through established diagnostic criteria. Despite this, a notable percentage of MO cases (10%-20%) remains unresolved after sequencing coding regions and copy number analysis of both genes.

Molecular and Phenotypic Characterization of the -Related Disorder.

Background And Objectives: Heterozygous variants in RAR-related orphan receptor B () have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with pathogenic variants and to provide arguments in favor of the pathogenicity of variants.

Four Novel Disease-Causing Variants in the Gene in Russian Patients with CADASIL.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease with unknown mechanisms and a broad phenotypic spectrum. It is caused by pathogenic variants in the gene. The symptoms of the disease mainly include recurrent strokes with vascular risk factors, migraine with aura, dementia, and mood disturbances.

Genetic and Clinical Spectrum of GNE Myopathy in Russia.

GNE myopathy (GNEM) is a rare hereditary disease, but at the same time, it is the most common distal myopathy in several countries due to a founder effect of some pathogenic variants in the gene. We collected the largest cohort of patients with GNEM from Russia and analyzed their mutational spectrum and clinical data. In our cohort, 10 novel variants were found, including 2 frameshift variants and 2 large deletions.

Case Report: Compound Heterozygous Variants of the Gene in a Russian Patient with Rafiq Syndrome.

Rafiq syndrome (RAFQS) is a congenital disorder of glycosylation (CDG) that is caused by mutations in the MAN1B1 gene and characterized by impaired protein and lipid glycosylation. RAFQS is characterized by a delay in intellectual and motor development, facial and other dysmorphism, truncal obesity, behavior problems, and hypotonia. We describe a Russian patient with delayed intellectual and motor development, a lack of speech, disorientation in space and time, impaired attention and memory, and episodes of aggression.

Clinical Manifestations of Various Molecular Cytogenetic Variants of Eight Cases of "8p Inverted Duplication/Deletion Syndrome".

Inverted duplication syndrome with an adjacent terminal deletion of the short arm of chromosome 8-inv dup del(8p)-is a rare complex structural chromosomal rearrangement with a wide range of clinical manifestations. Molecular cytogenetic variants of chromosomal imbalance depend on the mechanism of rearrangement formation. We analyzed the clinical-genetic and molecular cytogenetic characteristics of the 8p inverted duplication/deletion syndrome, as well as the genotype-phenotype correlation in eight unrelated cases with the rearrangement of inv dup del(8p).

Pediatric Encephalopathy: Clinical, Biochemical and Cellular Insights into the Role of Gln52 of and for the Dominant Disease.

Heterotrimeric G proteins are immediate transducers of G protein-coupled receptors-the biggest receptor family in metazoans-and play innumerate functions in health and disease. A set of de novo point mutations in and , the genes encoding the α-subunits (Gαo and Gαi1, respectively) of the heterotrimeric G proteins, have been described to cause pediatric encephalopathies represented by epileptic seizures, movement disorders, developmental delay, intellectual disability, and signs of neurodegeneration. Among such mutations, the Gln52Pro substitutions have been previously identified in and .

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability).

BH4-deficient hyperphenylalaninemia in Russia.

A timely detection of patients with tetrahydrobiopterin (BH4) -deficient types of hyperphenylalaninemia (HPABH4) is important for assignment of correct therapy, allowing to avoid complications. Often HPABH4 patients receive the same therapy as phenylalanine hydroxylase (PAH) -deficiency (phenylketonuria) patients-dietary treatment-and do not receive substitutive BH4 therapy until the diagnosis is confirmed by molecular genetic means. In this study, we present a cohort of 30 Russian patients with HPABH4 with detected variants in genes causing different types of HPA.

Retrospective analysis of 17 patients with mitochondrial membrane protein-associated neurodegeneration diagnosed in Russia.

Introduction: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological syndrome caused by pathogenic variants in the C19orf12 and is characterized by iron deposition in the basal ganglia and substantia nigra. Only a limited number of cohort studies were published to date and the prevalence of MPAN remains uncertain.

Methods: Recruited subjects with MPAN in Russia were diagnosed by whole-exome sequencing or Sanger sequencing of the C19orf12 gene.

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.

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.

Accurate fetal variant calling in the presence of maternal cell contamination.

High-throughput sequencing of fetal DNA is a promising and increasingly common method for the discovery of all (or all coding) genetic variants in the fetus, either as part of prenatal screening or diagnosis, or for genetic diagnosis of spontaneous abortions. In many cases, the fetal DNA (from chorionic villi, amniotic fluid, or abortive tissue) can be contaminated with maternal cells, resulting in the mixture of fetal and maternal DNA. This maternal cell contamination (MCC) undermines the assumption, made by traditional variant callers, that each allele in a heterozygous site is covered, on average, by 50% of the reads, and therefore can lead to erroneous genotype calls.

Spinocerebellar Ataxia-Like Presentation of the M233V PSEN1 Mutation.

PSEN1 gene is considered to be the most common gene, which is responsible for the development of an autosomal dominant Alzheimer disease with early onset and sometimes broad phenotype. We present a patient with a spinocerebellar ataxia (SCA)-like phenotype who was found to carry an M233V mutation. General and neurological exam was carried out.

Molecular and biochemical study of glutaric aciduria type 1 in 49 Russian families: nine novel mutations in the GCDH gene.

Glutaric aciduria type 1 (GA1, deficiency of glutaryl CoA dehydrogenase, glutaric acidemia type 1) (ICD-10 code: E72.3; MIM 231670) is an autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl CoA dehydrogenase (GCDH). Herein, we present the biochemical and molecular genetic characteristics of 51 patients diagnosed with GA1 from 49 unrelated families in Russia.

De novo nonsense mutation in WHSC1 (NSD2) in patient with intellectual disability and dysmorphic features.

Intellectual disability is the most common developmental disorder caused by chromosomal aberrations as well as single-nucleotide variants (SNVs) and small insertions/deletions (indels). Here we report identification of a novel, probably pathogenic mutation in the WHSC1 gene in a patient case with phenotype overlapping the features of Wolf-Hirschhorn syndrome. Deletions involving WHSC1 (Wolf-Hirschhorn syndrome candidate 1 gene) were described earlier in patients with Wolf-Hirschhorn syndrome.