Establishment of a Human iPSC Line from Mucolipidosis Type II That Expresses the Key Markers of the Disease.

Mucolipidosis type II (ML II) is a rare and fatal disease of acid hydrolase trafficking. It is caused by pathogenic variants in the gene, leading to the absence of GlcNAc-1-phosphotransferase activity, an enzyme that catalyzes the first step in the formation of the mannose 6-phosphate (M6P) tag, essential for the trafficking of most lysosomal hydrolases. Without M6P, these do not reach the lysosome, which accumulates undegraded substrates.

mRNA Degradation as a Therapeutic Solution for Mucopolysaccharidosis Type IIIC: Use of Antisense Oligonucleotides to Promote Downregulation of Heparan Sulfate Synthesis.

Mucopolysaccharidosis type IIIC is a neurodegenerative lysosomal storage disorder (LSD) characterized by the accumulation of undegraded heparan sulfate (HS) due to the lack of an enzyme responsible for its degradation: acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT). Classical treatments are ineffective. Here, we attempt a new approach in genetic medicine, genetic substrate reduction therapy (gSRT), to counteract this neurological disorder.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp.

Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

Introduction: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks.

The Biology of Lysosomes: From Order to Disorder.

Since its discovery in 1955, the understanding of the lysosome has continuously increased. Once considered a mere waste removal system, the lysosome is now recognised as a highly crucial cellular component for signalling and energy metabolism. This notable evolution raises the need for a summarized review of the lysosome's biology.

Induced pluripotent stem cell line (INSAi002-A) from a Fabry Disease patient hemizygote for the rare p.W287X mutation.

Fabry Disease (FD) is a multisystemic X-linked disorder that belongs to the group of lysosomal storage disorders (LSDs). Causal mutations on alpha-galactosidase A (α-Gal A) commonly lead to abnormal protein and consequently to FD. Since it is an X-linked disease, males are primarily affected.

Induced pluripotent stem cell line (INSAi001-A) from a Gaucher disease type 3 patient compound heterozygote for mutations in the GBA1 gene.

Gaucher Disease (GD) type 3 is a neurological form of a multisystemic autosomal recessive disorder belonging to the group of lysosomal storage diseases. Causal mutations in the glucocerebrosidase 1 (GBA1) commonly lead to abnormal protein and GD, heterozygosity is a genetic risk factor for Parkinson's disease. This work describes the use of a non-integrative approach using Sendai Virus delivery to establish induced Pluripotent Stem Cells (iPSCs) from fibroblasts from a GD type 3 patient.

In Silico Analysis of Missense Mutations as a First Step in Functional Studies: Examples from Two Sphingolipidoses.

In order to delineate a better approach to functional studies, we have selected 23 missense mutations distributed in different domains of two lysosomal enzymes, to be studied by in silico analysis. In silico analysis of mutations relies on computational modeling to predict their effects. Various computational platforms are currently available to check the probable causality of mutations encountered in patients at the protein and at the RNA levels.

Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy.

Unverricht-Lundborg disease (ULD) is a common form of progressive myoclonic epilepsy caused by mutations in the cystatin B gene () that encodes an inhibitor of several lysosomal cathepsins. Presently, only pharmacological treatment and psychosocial support are available for ULD patients. To overcome the pathogenic effect of the ULD splicing mutation c.

Mutation Frequency of Three Neurodegenerative Lysosomal Storage Diseases: From Screening to Treatment?

Background: The ascertainment of mutation frequencies in the general population may have impact on the population's wellbeing and respective healthcare services. Furthermore, it may help define which approaches will be more effective for certain patients based on the genetic cause of disease.

Aim Of The Study: Determine the frequency of three mutations, known to be a major cause of three distinct Lysosomal Storage Diseases (LSDs).

Characterization of a rare Unverricht-Lundborg disease mutation.

Cystatin B (CSTB) gene mutations cause Unverricht-Lundborg disease (ULD), a rare form of myoclonic epilepsy. The previous identification of a Portuguese patient, homozygous for a unique splicing defect (c.66G > A; p.

Efficient IDUA Gene Mutation Detection with Combined Use of dHPLC and Dried Blood Samples.

Objectives. Development of a simple mutation directed method in order to allow lowering the cost of mutation testing using an easily obtainable biological material. Assessment of the feasibility of such method was tested using a GC-rich amplicon.

CHIT1 genetic defects in the Portuguese population.

Chitotriosidase is an enzyme secreted by activated macrophages and a useful biomarker in several lysosomal and nonlysosomal diseases. However, chitotriosidase gene (CHIT1) mutations may lead to inaccuracy in the significance of this biomarker. Reports on the molecular spectrum of genetic variation in chitotriosidase are rare, and this is one of the few that focus on a specific population group.

Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases.