XYLT2

Desbuquois dysplasia type 2 (DBQD2) and spondylo-ocular syndrome (SOS) are autosomal recessive disorders affecting the extracellular matrix (ECM) and categorized as glycosaminoglycan (GAG) linkeropathies. Linkeropathies result from mutations within glycosyltransferases involved in the synthesis of the tetrasaccharide linker, a linker between the core protein of proteoglycan (PG) and GAG. DBQD2 and SOS are caused by the isolated mutations of the xylosyltransferase (XT) isoforms. In this work, we successfully generated XYLT1 - as well as XYLT2 -deficient GAG linkeropathy model systems in human dermal fibroblasts using a ribonucleoprotein-based CRISPR/Cas9-system...

Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations...

pax6 is a canonic master gene for eye formation. Knockout of pax6 affects the development of craniofacial skeleton and eye in mice. Whether pax6 affects the development of spinal bone has not been reported yet. In the present study, we used CRISPR/Cas9 system to generate Olpax6.1 mutant in Japanese medaka. Phenotype analysis showed that ocular mutation caused by the Olpax6.1 mutation occurred in the homozygous mutant. The phenotype of heterozygotes is not significantly different from that of wild-type. In addition, knockout Olpax6...

Spondyloocular syndrome (SOS, OMIM # 605822) is a rare genetic disorder characterized by osseous and ocular manifestations, including generalized osteoporosis, multiple long bones fractures, platyspondyly, dense cataracts and retinal detachment, and dysmorphic facial features, with or without short stature, cardiopathy, hearing impairment, and intellectual disability. Biallelic mutations in the XYLT2 gene (OMIM * 608125), encoding the xylosyltransferase II, were shown to be responsible for this disease. To date, 22 cases with SOS have been described, with varying clinical presentations and a yet-to-be-established genotypic-phenotypic correlation...

The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation. Furthermore, XT-I overexpression is associated with fibrosis, whereby a fibrotic process initially develops from a dysregulated wound healing. In a physiologically wound healing process, extracellular matrix-producing myofibroblasts enter acute senescence to protect against fibrosis. The aim of this study was to determine the role of XT-I in acute senescent proto-myofibroblasts...

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles...

[This corrects the article DOI: 10.3389/fgene.2021.761264.].

The total milk production of India is 209.96 MT out of which 45% is contributed by the indigenous buffalo and due to their high producing virtue, the prevalence of mastitis is 5-20%. Despite the increasing level of technological advancement, mastitis is still an issue of concern for dairy industry in India as well as across the world. Therefore, the present study aimed to identify the SNPs and associate them with the incidence of clinical mastitis in Murrah buffalo using the ddRAD sequencing approach taking mastitis incidence data of 96 Murrah buffaloes...

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has infected millions worldwide. SARS-CoV-2 spike protein uses Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) for entering and fusing the host cell membrane. However, interaction with spike protein receptors and protease processing are not the only factors determining coronaviruses' entry. Several proteases mediate the entry of SARS-CoV-2 virus into the host cell...

Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with a high mortality rate. Glycolysis is an important pathway for tumors to obtain energy. However, its role in CC remains largely unknown. In present study, we analyzed glycolysis-related gene expression to depict clinical characteristics and its relationship with tumor immunity in CC to find potential target treatments. A prognostic model based on 13 glycolysis-related genes was established by univariate and multivariate Cox regression analyses...

Spondyloocular syndrome (SOS) is a skeletal disorder caused by pathogenic variants in XYLT2 gene encoding a xylotransferase involved in the biosynthesis of proteoglycans. This condition, with autosomal recessive inheritance, has a high phenotypic variability. It is characterized by bone abnormalities (osteoporosis, fractures), eye and cardiac defects, hearing impairment, and varying degrees of developmental delay. Until now only 20 mutated individuals have been reported worldwide. Here, we describe two siblings from consanguineous healthy parents in which a novel homozygous frameshift variant c...

The role of long noncoding RNAs- (lncRNAs-) associated competing endogenous RNA (ceRNA) in the field of hepatocellular carcinoma (HCC) biology is well established, but the involvement of lncRNAs competing interactions in the progression of liver cirrhosis to HCC is still unclear. We aimed to explore the differential expression profiles of lncRNAs, microRNAs (miRNA), and messenger RNAs (mRNAs) to construct a functional ceRNA network in cirrhotic HCC. The lncRNA, miRNA, and mRNA expression datasets were obtained from Gene Expression Omnibus and The Cancer Genome Atlas...

In this paper we characterize the function of Xylosyltransferase 2 (XylT2) in different tissues to investigate the role XylT2 has in the proteoglycan (PG) biochemistry of multiple organs. The results show that in all organs examined there is a widespread and significant decrease in total XylT activity in Xylt2 knock out mice (Xylt2-/-). This decrease results in increased organ weight differences in lung, heart, and spleen. These findings, in addition to our previous findings of increased liver and kidney weight with loss of serum XylT activity, suggest systemic changes in organ function due to loss of XylT2 activity...

Proteoglycans (PGs) are glycoconjugates which are predominately expressed on cell surfaces and consist of glycosaminoglycans (GAGs) linked to a core protein. An initial step of GAGs assembly is governed by the β-D-xylosyltransferase enzymes encoded in mammals by the XylT1/XylT2 genes. PGs are essential for the interaction of a cell with other cells as well as with the extracellular matrix. A number of studies highlighted a role of PGs in bacterial adhesion, invasion, and immune response. In this work, we investigated a role of PGs in Salmonella enterica serovar Typhimurium ( S ...

Fibrosis is a fundamental feature of systemic sclerosis (SSc) and is characterized by excessive accumulation of extracellular matrix components like proteoglycans (PG) or collagens in skin and internal organs. Serum analysis from SSc patients showed an increase in the enzyme activity of xylosyltransferase (XT), the initial enzyme in PG biosynthesis. There are two distinct XT isoforms-XT-I and XT-II-in humans, but until now only XT-I is associated with fibrotic remodelling for an unknown reason. The aim of this study was to identify new XT mediators and clarify the underlying mechanisms, in view of developing putative therapeutic anti-fibrotic interventions in the future...

Human xylosyltransferases-I and -II (XT-I and XT-II) catalyze the initial and rate-limiting step in proteoglycan (PG)-biosynthesis. Because PG are major components of the extracellular matrix (ECM), an alternated XT expression is associated with the manifestation of ECM-related diseases. While Drosophila melanogaster and Caenorhabditis elegans only harbor one XT-isoform, all higher organisms contain two isoforms, which are expressed in a tissue-specific manner. The reason for the appearance of two isoenzymes remains unexplained and remarkable, as all other enzymes involved in the synthesis of the tetrasaccharid linker, which connects the PG core protein with attached glycosaminoglycans, only show one isoform...

The term linkeropathies (LKs) refers to a group of rare heritable connective tissue disorders, characterized by a variable degree of short stature, skeletal dysplasia, joint laxity, cutaneous anomalies, dysmorphism, heart malformation, and developmental delay. The LK genes encode for enzymes that add glycosaminoglycan chains onto proteoglycans via a common tetrasaccharide linker region. Biallelic variants in XYLT1 and XYLT2, encoding xylosyltransferases, are associated with Desbuquois dysplasia type 2 and spondylo-ocular syndrome, respectively...

We report on three new patients with spondyloocular syndrome (SOS) in a consanguineous Pakistani family. All three patients present progressive generalized osteoporosis, short stature, recurrent fractures, hearing loss and visual impairments. WES revealed a novel homozygous frameshift variant in exon 11 of XYLT2 (NG 012175.1, NP_071450.2) resulting in loss of evolutionary conserved amino acid sequences (840 - 865/865) at C-terminus p.R840fs∗ 115. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients while the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern...

Rubinstein-Taybi syndrome (RSTS) is an autosomal-dominant neurodevelopmental disease affecting 1:125,000 newborns characterized by intellectual disability, growth retardation, facial dysmorphisms and skeletal abnormalities. RSTS is caused by mutations in genes encoding for writers of the epigenetic machinery: CREBBP (~ 60%) or its homologous EP300 (~ 10%). No causative mutation is identified in up to 30% of patients. We performed whole-exome sequencing (WES) on eight RSTS-like individuals who had normal high-resolution array CGH testing and were CREBBP- and EP300-mutation -negative, to identify the molecular cause...

BACKGROUND/OBJECTIVES: The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipose tissue homeostasis...