Jph3

BACKGROUND: Huntington's disease like 2 (HDL2) has been reported exclusively in patients with African ancestry, mostly originating from South Africa. CASE REPORT: We report three patients in Mali including a proband and his two children who have been examined by neurologists and psychiatrists after giving consent. They were aged between 28 and 56 years old. Psychiatric symptoms were predominant in the two younger patients while the father presented mainly with motor symptoms...

BACKGROUND: Colorectal cancer (CRC), is the third most prevalent cancer across the globe, and is often detected at advanced stage. Late diagnosis of CRC, leave the chemotherapy and radiotherapy as the main options for the possible treatment of the disease which are associated with severe side effects. In the present study, we seek to explore CRC gene expression data using a systems biology framework to identify potential biomarkers and therapeutic targets for earlier diagnosis and treatment of the disease...

Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation. Nevertheless, outside South Africa, reports of patients with HDL2 in Africa are scarce, probably owing to limited clinical services across the continent...

Periparturient hypocalcemia is a complex metabolic disorder that occurs at the onset of lactation because of a sudden irreversible loss of Ca incorporated into colostrum and milk. Some cows are unable to quickly adapt to this demand and succumb to clinical hypocalcemia, commonly known as milk fever, whereas a larger proportion of cows develop subclinical hypocalcemia. The main goal of this study was to identify causative mutations and candidate genes affecting postpartum blood calcium concentration in Holstein cows...

BACKGROUND: Sarcopenia is a disease diagnosed in the elderly. In patients with sarcopenia, the muscle mass decreases every year. The occurrence of sarcopenia is greatly affected by extrinsic factors such as eating habits, exercise, and lifestyle. The present study aimed to determine the relationship between muscle mass traits and genes affected by epigenetic factors with three different adjustment methods using Korean Genome and Epidemiology Study (KOGES) data. RESULTS: We conducted a demographic study and DNA methylation profiling by three studies according to the muscle mass index (MMI) adjustment methods: appendicular skeletal muscle mass divided by body weight (MMI1); appendicular skeletal muscle mass divided by square of height (MMI2); appendicular skeletal muscle mass divided by BMI (MMI3)...

DNA methylation studies of incident type 2 diabetes in US populations are limited, and to our knowledge none included individuals of African descent living in the US. We performed an epigenome-wide association analysis of blood-based methylation levels at CpG sites with incident type 2 diabetes using Cox regression in 2,091 Black and 1,029 White individuals from the Atherosclerosis Risk in Communities study. At an epigenome-wide significance threshold of 10 -7 , we detected 7 novel diabetes-associated CpG sites in C1orf151 (cg05380846: HR= 0...

BACKGROUND: CXCL12 is a vital factor in physiological and pathological processes, by inducing migration of multiple cells. We aimed to comprehensively detect the role of CXCL12 in breast cancer, and explore novel CXCL12-related biomarkers through integrative multi-omics analyses to build a powerful prognostic model for breast cancer patients. METHODS: Immunohistochemistry analysis of the tissue microarray was performed to evaluate the correlation between CXCL12 expression levels and breast cancer patient outcomes...

Chorea, cognitive decline, and psychiatric symptoms are shared by Huntington's disease (HD) and similar conditions called HD phenocopies. We describe the first case reported in Italy of Huntington disease-like 2 (HDL2), clinically and radiologically indistinguishable from HD, showing the importance of considering African ancestry in the diagnostic process.

INTRODUCTION: There are reports of different clinical statuses in carriers of intermediate alleles (IAs) of CAG trinucleotide repeats in the HTT gene, from individuals affected by a clinical picture indistinguishable from Huntington's disease (HD) to those without manifestations. Therefore, the possible clinical significance of these alleles has been widely debated. OBJECTIVES: To describe general and clinical features and discard HD phenocopies by molecular assessment in a case series of IA carriers on the HTT gene of a laboratory sample from a neurological center in Mexico...

Glioblastoma multiforme (GBM) has been identified as a frequently occurring adult primary brain cancer that is highly aggressive. Currently, the prognostic outcome for GBM patients is dismal, even with intensive treatment, and the median overall survival (OS) is 14.6 months. Immunotherapy, which is specific at the cellular level and can generate persistent immunosurveillance, is now becoming a promising tool to treat diverse cancers. However, the complicated nature of the tumor microenvironment (TME) makes it challenging to develop anti-GBM immunotherapy because several cell types, cytokines, and signaling pathways are involved in generating the immunosuppressive environment...

BACKGROUND: Early screening is the most effective way to control breast cancer. Due to the lack of accurate biomarkers, early diagnosis of breast cancer is still very difficult. Therefore, it is necessary to discover new candidate genes of breast cancer and improve the early diagnosis and prognosis. METHODS: A DO-UniBIC gene screening method was proposed. First, Disease Ontology (DO) analysis was used to screen out breast cancer related genes from differentially expressed genes, and then the UniBIC algorithm was used to find all gene clusters with the same changing trend based on the longest common subsequence...

In skeletal muscle, depolarization of the plasma membrane (PM) causes conformational changes of the calcium channel CaV1.1 that then activate RYR1 to release calcium from the SR. Being independent of extracellular calcium entry, this process is termed voltage-induced calcium release. In skeletal muscle, junctophilins (JPHs) 1 and 2 form the SR-PM junctions at which voltage-induced calcium release occurs. Previous work demonstrated that JPH2 is able to recapitulate voltage-induced calcium release when expressed in HEK293 cells together with CaV1...

Junctophilins (JPHs) comprise a family of structural proteins that connect the plasma membrane to intracellular organelles such as the endo/sarcoplasmic reticulum. Tethering of these membrane structures results in the formation of highly organized subcellular junctions that play important signaling roles in all excitable cell types. There are four JPH isoforms, expressed primarily in muscle and neuronal cell types. Each JPH protein consists of 6 'membrane occupation and recognition nexus' (MORN) motifs, a joining region connecting these to another set of 2 MORN motifs, a putative alpha-helical region, a divergent region exhibiting low homology between JPH isoforms, and a carboxy-terminal transmembrane region anchoring into the ER/SR membrane...

In skeletal muscle, depolarization of the plasma membrane (PM) causes conformational changes of the calcium channel CaV1.1, which then activate RYR1 to release calcium from the sarcoplasmic reticulum (SR). Because it does not require extracellular calcium entry, this process is termed voltage-induced calcium release. In skeletal muscle, junctophilins (JPH) 1 and 2 are responsible for forming the SR-PM junctions at which voltage-induced calcium release occurs; structurally similar junctions with different molecular constituents are formed in neurons by JPH3 and JPH4...

Junctophilin-3 belongs to a triprotein junctional complex implicated in the regulation of neuronal excitability and involved in the formation of junctional membrane structures between voltage-gated ion channels and endoplasmic (ryanodine) reticular receptors. A monoallelic trinucleotide repeat expansion located within the junctophilin-3 gene (JPH3) has been implicated in a rare autosomal dominant (AD) late-onset (and progressive) disorder clinically resembling Huntington disease (HD), and known as HD-like 2 (HDL2; MIM# 606438)...

Background: Tumor microenvironment (TME) is closely related to the progression of glioma and the therapeutic effect of drugs on this cancer. The aim of this study was to develop a signature associated with the tumor immune microenvironment using machine learning. Methods: We downloaded the transcriptomic and clinical data of glioma patients from the Chinese Glioma Genome Atlas (CGGA) databases (mRNAseq_693). The single-sample Gene Set Enrichment Analysis (ssGSEA) database was used to quantify the relative abundance of immune cells...

Despite their recognized physiological importance, the molecular architecture of ER-PM junctions induced by neuronal junctophilins (JPH3 and JPH4) is still poorly understood and challenging to address in neurons. This is due to the small size of the junctions and to the multiple isoforms of candidate junctional proteins in different brain areas. Using colocalization of tagged proteins expressed in tsA201 cells, and electrophysiology, we compared the interactions of JPH3 and JPH4 with different calcium channels...

BACKGROUND: The diagnostic workup for choreiform movement disorders including Huntington's disease (HD) and those mimicking HD like phenotype is complex. OBJECTIVE: The aim of the present study was to genetically define HD and HD-like presentations in an Indian cohort. We also describe HTT-CAG expansion manifesting as neuroferritinopathy-like disorder in four families from Punjab in India. MATERIALS AND METHODS: 159 patients clinically diagnosed as HD and HD-like presentations from various tertiary neurology clinics were referred to our centre (CSIR-IGIB) for genetic investigations...

Glioma, a common malignant tumor of the central nervous system, is of high invasiveness. The objective of this study was to identify genes playing an important role in the development of glioma and to reveal their potential research value. Conjoint analysis on the GSE16011 data set in the Gene Expression Omnibus (GEO) database and the "Messenger RNA Expression Microarray of Diffuse Gliomas and Controls" data set and "RNA sequencing of Diffuse Gliomas" data set in the Chinese Glioma Genome Atlas (CGGA) database is carried out in the study...

OBJECTIVES: Huntington's Disease Like-2 (HDL2) is a rare autosomal dominant genetic disease caused by a mutation in the JPH3 gene. The Huntington's Disease (HD) phenocopy has the greatest clinical resemblance to HD, but its neurocognitive characterisation is poorly researched. This study reports on the neurocognitive profile of seven HDL2 patients including preserved functions, deficits and dissociations (classical and strong) and provides a general characterisation of the cognitive dysfunction of HDL2 in relation to the progression of the disease...