Project description:Trigeminal neuralgia (TN) is a type of neuropathic pain caused by injury to sensory nerves, manifesting as severe paroxysmal pain of the head and face. Trigeminal neuralgia brings a huge burden to patients, without long-term effective treatment. Changes in the expression of pain-related genes in the whole blood samples of patients play an important role in the pathogenesis, diagnosis, and evaluation of treatment effects of trigeminal neuralgia. To better understand the mechanism of trigeminal neuralgia, we collect the whole blood samples from the trigeminal neuralgia patients and the pain-free healthy comparisons. RNA-seq was conducted between the two groups to find the transcriptome changes in patients with trigeminal neuralgia.
Project description:<p>AHC is a rare and severe neurological disorder, and characterized by episodic hemiplegia or quadriplegia attacks, accompanied by other paroxysmal symptoms of oculomotor abnormalities, dystonia, seizures and autonomic disturbances; the age of onset usually occurrs before 18 months of life. Sodium-potassium ATPase alpha3 subunit (ATP1A3) has recently been identified as a causal gene for sporadic AHC by three groups. However, there has not been any large genetic study on a Chinese cohort.</p> <p>In the submitted data, whole-exome sequencing of three trios and three sporadic cases in a Chinese cohort produced an average of 18.8 gigabases of raw sequence. Through our analysis pipeline including BWA mapping, GATK recalibration, variant calling and filtering, all six patients contained missense mutations in ATP1A3 which were further confirmed as <i>de novo</i> mutations. Along with validation in additional patients, this study confirmed ATP1A3 as a causal gene in Chinese AHC patients, and reported six novel mutations. </p>
Project description:Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord. Inhibition of microglia activation and neutralization of IL-1β also attenuated neuropathic pain in NMOSD rat model. In addition, the human CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis and other neurological disorder patients. These findings indicate ATP, microglial activation and IL-1β secretion orchestrates the pathogenesis of NMOSD neuropathic pain.
Project description:Bipolar disorder (BD) is a psychiatric disorder in which the core feature is pathological disturbance in mood ranging from extreme elation (mania) to severe depression. Study has shown an aberrant pro-inflammatory status of monocytes/macrophages in mood disorders. Therefore, this study aimed at studying the monocyte compartment in Bipolar Disorder, by transcription profiling of CD14+ monocytes in patients and controls.
Project description:Peripheral neuropathic pain remains challenging to treat, partly due to our limited understanding of the molecular mechanisms at play in humans. In this multicentre cohort study, we describe the local molecular signature of neuropathic pain at the lesion site, using peripheral nerves of patients with Morton’s neuroma a s a human model system of neuropathic pain. Plantar tibial nerves were collected from 22 patients with Morton's neuroma and control nerves from 11 participants without a nerve injury. Pre-surgery, we collected data on pain severity, duration and nature (e.g., neuropathic pain inventory, NPSI). RNA bulk sequencing of peripheral nerves identified 3349 genes to be differentially expressed between Morton's neuroma and controls. Gene ontology enrichment analysis and weighted gene co-expression network analyses (WGCNA) identified over-representation of biological processes related to the inflammatory response, axon guidance and myelination. WGCNA modules specific for the defense and immune responses and neurogenesis. Modules associated with defense response, angiogenesis and muscle system development were correlated with NPSI paroxysmal and evoked pain in Morton’s neuroma patients. Deconvolution analysis confirmed that the densities of M1 and M2 macrophages as well as B-cells were higher in Morton’s neuroma than control samples. The findings for T-cells were inconclusive, and dependent on the reference gene signature used. Immunofluorescent analyses confirmed the presence of demyelination and higher densities of intraneural T-cells in Morton’s neuroma sections compared to control nerves. Our findings provide detailed insight into the local molecular signature in the context of human focal nerve injury. There is clear evidence for an ongoing role of the immune system in chronic peripheral neuropathic pain in humans.
Project description:We performed a targeted NGS using the commercial gene panel design ClearSeq Inherited Disease (Agilent Technologies) to identify the pathogenic sequence variants in a girl presenting an apparent microcephaly with mild dysmorphic facial features, delayed psychomotoric development and central hypotonia.
Project description:Fibromyalgia is a complex disorder characterized by increased sensitivity to pain and extreme tiredness. It affects mostly women, and its causes are unknown.
In this study we have performed exome sequencing of 87 fibromyalgia cases, including some sibling pairs, to perform rare variant association analysis and identify fibromyalgia risk factors.
A few of the included samples have been also included in a previous GWAS study.
Project description:Interstitial cystitis (IC) and bladder pain syndrome are terms used to describe a heterogenous chronic pelvic and bladder pain disorder of unknown etiology. The goal of this pilot study was to determine if gene expression profiling of bladder biopsy tissue from patients experiencing symptoms could be used to separate the patients based on some clinical parameter.
Project description:SEM cells were established from the peripheral blood of a 5-year-old girl in relapse with acute lymphoblastic leukaemia (ALL). SEM cells exhibit the t(4;11) chromosomal rearrangement, which leads to production of the MLL-AF4 fusion protein. Hematopoietic transcription factors including HOXA9 and MEIS1 are highly expressed in ALL.
Project description:Whole exome sequencing to identify potentially relevant mutations of congenital cataract in a Chinese girl.
The novel PAX6 mutation (c.221G>A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) interactively aggravates this process.