Prenatal Diagnosis of Mucopolysaccharidosis-Plus Syndrome (MPSPS).

Mucopolysaccharidosis-plus syndrome (MPSPS) is an autosomal-recessive disorder caused by c.1492C>T (p.R498W) in the gene.

A Case of Mucopolysaccharidosis II Caused by a Novel Variant with Skin Linear Hyperpigmented Streaks along Blaschko's Lines.

We report a case of an eight-year-old boy with mucopolysaccharidosis (MPS) II with atypical skin lesions of hyperpigmented streaks along Blaschko's lines. This case presented with mild symptoms of MPS such as hepatosplenomegaly, joint stiffness, and quite mild bone deformity, which was the reason for the delay in diagnosis until the age of seven years. However, he showed an intellectual disability that did not meet the diagnostic criteria for an attenuated form of MPS II.

Origins of SOPH syndrome: A study of 93 Yakut patients with review of C-terminal phenotype.

Since the first report of SOPH syndrome among the Yakut population in 2010, new clinical data of SOPH-like conditions continue to appear. We expand the phenotypic spectrum of SOPH syndrome and perform a comparative analysis of Yakut SOPH patients' clinical data with SOPH-like conditions reported in the world scientific literature to form a foundation for NBAS pathogenesis discussion. Clinical data from the genetic records of 93 patients with SOPH syndrome and global survey data on patients with pathogenic variants of the C-terminal in the NBAS gene were collected.

Hematopoietic Disorders, Renal Impairment and Growth in Mucopolysaccharidosis-Plus Syndrome.

Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders (LSD) characterized by the excessive accumulation of glycosaminoglycans (GAG). Conventional MPS, caused by inborn deficiencies of lysosomal enzymes involved in GAG degradation, display various multisystemic symptoms-including progressive neurological complications, ophthalmological disorders, hearing loss, gastrointestinal and hepatobiliary issues, cardiorespiratory problems, bone and joint abnormalities, dwarfism, and coarse facial features. Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease caused by a mutation in the endo-lysosomal tethering protein VPS33A, shows additional renal and hematopoietic abnormalities ("Plus symptoms") uncommon in conventional MPS.

[Clinical and genetic description of neuronal ceroid lipofuscinosis 6 type in the yakut family].

Neuronal ceroid lipofuscinosis type 6 (NCL 6) is a rare progressive neurodegenerative disease that belongs to the group of lysosomal storage diseases. A clinical and genetic description of NCL 6 in a Yakut family was carried out. The proband and her sibling showed characteristic clinical signs, including myoclonic epilepsy, ataxia, psychomotor regression, dementia, and visual impairment.

Pilot Screening of Cell-Free mtDNA in NIPT: Quality Control, Variant Calling, and Haplogroup Determination.

Clinical tests based on whole-genome sequencing are generally focused on a single task approach, testing one or several parameters, although whole-genome sequencing (WGS) provides us with large data sets that can be used for many supportive analyses. In spite of low genome coverage, data of WGS-based non-invasive prenatal testing (NIPT) contain fully sequenced mitochondrial DNA (mtDNA). This mtDNA can be used for variant calling, ancestry analysis, population studies and other approaches that extend NIPT functionality.

Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy.

The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns.

Mucopolysaccharidosis-Plus Syndrome.

Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes-mucopolysaccharidosis-plus syndrome (MPSPS). MPSPS, whose pathophysiology is not elucidated, is an autosomal recessive multisystem disorder caused by a specific mutation p.R498W in the gene.

Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms.

Mucopolysaccharidoses (MPS) are a group of genetic deficiencies of lysosomal enzymes that catabolize glycosaminoglycans (GAG). Here we describe a novel MPS-like disease caused by a specific mutation in the VPS33A gene. We identified several Yakut patients showing typical manifestations of MPS: coarse facial features, skeletal abnormalities, hepatosplenomegaly, respiratory problems, mental retardation, and excess secretion of urinary GAG.

A novel homozygous mutation causing hereditary tyrosinemia type I in yakut patient in russia: case report.

Introduction: Tyrosinemia type 1 (HT1) (OM IM 276700) is an inborn error of tyrosine catabolism caused be fumarylacetoacetate hedralase deficiency (FAH). In tyrosinemia type I, dietary therapy and nitisinone (Orfandin®), liver transplantation are effective .

Aim: We present here the first report on identification of FAH mutation in HT1 Yakut patient from Russia with a novel one.

[Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.

Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.

Background: Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision.

Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia.

Background: In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified.

Methods: Because Yakuts are considered as a population isolate and the disease is rare in other populations, genomewide homozygosity mapping was performed using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut.

Results: All families shared an identical haplotype in the same region as the identical loci responsible for 3-M and gloomy face syndromes and a novel homozygous 4582insT mutation in Cullin 7 (CUL7) was found, which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 (Q1553X).