[A case of rare hereditary Siddiqi syndrome with novel neuropsychiatric signs].

A fifth world case of autosomal recessive Siddiqi syndrome (SIDDIS) related to ene is presented. In a consanguineous Lezgin (a Dagestan ethnicity) family, there were two affected brothers aged 28 yrs (proband, personally examined) and 32 yrs. Whole-exome sequencing followed by familial Sanger sequencing detected a novel missence variant c.

Clinical and Genetic Analysis of Digenic Muscular Dystrophy due to SRPK3 and TTN Variants in Two Siblings.

We present a family with two male siblings diagnosed with a newly described digenic myopathy, involving likely pathogenic loss-of-function variants in the SRPK3 and TTN genes: hemizygous p.(Pro68ArgfsTer55) and heterozygous p.(Trp14174Ter), respectively.

Case Report: Exploring the clinical spectrum of LGMD R27: insights from a case study with homozygous pathogenic variant in the gene.

Limb-girdle muscular dystrophies (LGMD) constitute a heterogeneous group of genetic disorders characterized by progressive muscle weakness and atrophy, predominantly affecting the muscles of the pelvic and shoulder girdles. LGMD R27, linked to biallelic pathogenic variants in the gene, was recently described, and to date, only 27 cases has been published in three reports. Here, we present two siblings exhibiting a severe clinical phenotype of LGMD R27, associated with a novel homozygous frameshift variant [c.

CAG Polymorphic Locus of Androgen Receptor () Gene in Russian Infertile and Fertile Men.

The androgen receptor (AR) is critical for mediating the effects of androgens. The polymorphic CAG locus in exon 1 of the gene is associated with several diseases, including spinal and bulbar muscular atrophy (SBMA), prostate cancer, and male infertility. This study evaluated the CAG locus in 9000 infertile Russian men and 286 fertile men (control group).

Common Variants in the Gene with Unclear Pathogenicity as the Cause of Oculocutaneous Albinism in a Cohort of Russian Patients.

oculocutaneous albinism (OCA) is a hereditary impairment of skin, hair, and eye pigmentation. The most common form of albinism is autosomal recessive albinism, caused by mutations in the gene, accounting for approximately 40-50% of all cases of the disease in European populations. Common hypomorphic variants in the gene could lead to a mild form of albinism in a compound heterozygous state with a pathogenic variant.

Challenging Diagnosis of a Patient with Two Novel Variants in the Gene.

We report a case of -associated autosomal recessive spinocerebellar ataxia (SCAR8) presenting with a complex multisystemic phenotype, including highly elevated creatine kinase levels and lower-leg muscle atrophy. In addition to identifying two novel pathogenic variants in the gene, whole-exome sequencing revealed three variants of uncertain significance in the gene. Electromyography and muscle magnetic resonance imaging indicated a neurogenic pattern of muscle involvement.

The Study of the Inheritance Mechanisms of Myotonic Dystrophy Type 1 (DM1) in Families from the Republic of North Ossetia-Alania.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder with progressive myopathy and myotonia. The clinical study was conducted in the Republic of North Ossetia-Alania (RNOA), and in it 39 individuals from 17 unrelated families were identified with DM1. Clinical presentations varied, including muscle weakness, fatigue, intellectual disability, hypersomnia, ophthalmological abnormalities, and alopecia.

Asymmetric scapuloperoneal phenotype of -related distal myopathy: case series.

Recent research has sparked a discussion on the spectrum of diseases linked to the gene associated with amyotrophic lateral sclerosis and distal myopathy with vocal cord and pharyngeal weakness (VCPDM). To date, fewer than 50 cases of VCPDM have been reported in the literature. We aim to build upon the work of previous researchers by gathering additional information about VCPDM.

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.

Rare Variants of the Gene Detected during Neonatal Screening.

During the expanded neonatal screening program conducted in 2023, we analyzed samples obtained from 1,227,130 out of 1,256,187 newborns in the Russian Federation in order to detect 5q spinal muscular atrophy (5q SMA). Within the 253-sample risk group formed based on the results of the first screening stage, 5 samples showed a discrepancy between the examination results obtained via various screening methods and quantitative MLPA (used as reference). The discrepancy between the results was caused by the presence of either a c.

Presentation of Rare Phenotypes Associated with the Gene.

Pathogenic variants in the gene lead to a spectrum of rare autosomal recessive phenotypes, including osteogenesis imperfecta (OI) Type XI, Bruck syndrome Type I (BS I), and the congenital arthrogryposis-like phenotype (AG), each with variable clinical manifestations that are crucial for diagnosis. This study analyzed the clinical-genetic characteristics of patients with these conditions, focusing on both known and newly identified variants. We examined data from 15 patients, presenting symptoms of OI and joint contractures.

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.

Generation of induced pluripotent stem cell line (RCMGi012-A) from fibroblasts of patient with mucopolysaccharidosis type VI.

Skin fibroblasts obtained from a 5-year-old girl with genetically proven (two heterozygous mutations in ARSB gene) and clinically manifested mucopolysaccharidosis type VI were successfully transformed into induced pluripotent stem cells by using Sendai virus-based reprogramming vectors including the four Yamanaka factors namely SOX2, OCT3/4, KLF4, and c-MYC. These iPSCs expressed pluripotency markers, had a normal karyotype and the potential to differentiate into three germ layers in spontaneous differentiation assay. The line may be used for cell differentiation and pharmacological investigations, and also may provide a model for development of a personalized treatment including drug screening and genome editing.

Pathogenic Variants and Genotypes of the Gene in Russian Men with Cystic Fibrosis and CBAVD Syndrome.

Pathogenic variants cause cystic fibrosis (CF), and CF-related disorders (CF-RD), including bilateral aplasia of the vas deferens (CBAVD). The spectrum of clinical manifestations depends on the genotype. The frequency and spectrum of the variants vary between populations and clinical groups.

A Molecular Genetic Analysis of RPE65-Associated Forms of Inherited Retinal Degenerations in the Russian Federation.

Unlabelled: Pathogenic variants in the gene cause the only known form of inherited retinal degenerations (IRDs) that are prone to gene therapy. The current study is aimed at the evaluation of the prevalence of RPE65-associated retinopathy in the Russian Federation, the characterization of known variants in the gene, and the establishment of the specificities of the mutation spectrum in Russian patients.

Methods: The analysis was carried out on blood samples obtained from 1053 non-related IRDs patients.

GABRA1-Related Disorders: From Genetic to Functional Pathways.

Objective: Variants in GABRA1 have been associated with a broad epilepsy spectrum, ranging from genetic generalized epilepsies to developmental and epileptic encephalopathies. However, our understanding of what determines the phenotype severity and best treatment options remains inadequate. We therefore aimed to analyze the electroclinical features and the functional effects of GABRA1 variants to establish genotype-phenotype correlations.

Step-by-Step Double-Trouble OBAIRH and DMD Diagnosis in a One-Year-Old Boy.

We present a case of a combination of two rare hereditary disorders: obesity, adrenal insufficiency and red hair syndrome (OBAIRH) and Duchenne muscular dystrophy (DMD) in a boy. Both diseases were diagnosed during the first year of life. OBAIRH was suggested based on the ethnicity and family history of the patient, while DMD was based on an extreme increase in transaminase and CK (creatine kinase) levels during a biochemical analysis of his blood.

L138ins Variant of the Gene in Russian Infertile Men.

(1) Introduction: Pathogenic variants in the (Cystic Fibrosis Transmembrane conductance Regulator, OMIM: 602421) gene cause Cystic Fibrosis (CF, OMIM: 219700) and CF-related disorders (CF-RD), often accompanied by obstructive azoospermia due to congenital bilateral aplasia of vas deferens (CBAVD, OMIM: 277180) in male patients. The L138ins (c.413_415dup; p.

Evaluation of Pathogenicity and Causativity of Variants in the and Genes in a Family Case of Hereditary Peripheral Neuropathy.

The implementation of NGS methods into clinical practice allowed researchers effectively to establish the molecular cause of a disorder in cases of a genetically heterogeneous pathology. In cases of several potentially causative variants, we need additional analysis that can help in choosing a proper causative variant. In the current study, we described a family case of hereditary motor and sensory neuropathy (HMSN) type 1 (Charcot-Marie-Tooth disease).