Cerebral vascular malformations: pathogenesis and therapy.

Cerebral vascular malformations (CVMs), particularly cerebral cavernous malformations and cerebral arteriovenous malformations, pose significant neurological challenges due to their complex etiologies and clinical implications. Traditionally viewed as congenital conditions with structural abnormalities, CVMs have been treated primarily through resection, embolization, and stereotactic radiosurgery. While these approaches offer some efficacy, they often pose risks to neurological integrity due to their invasive nature.

A rare Coffin-Siris syndrome induced by SOX11: a de novo nonsense variant of short stature.

Background: Coffin-Siris syndrome is a clinically elusive and rare genetic disease characterized by a wide range of clinical manifestations. This study deeply analyzed and identified the clinical phenotype and genetic variant location in a pediatric patient with Coffin-Siris syndrome, aiming to enhance the understanding of this syndrome and assist in its screening and diagnosis.

Methods: A combination of advanced diagnostic tools, including high-throughput whole-exome sequencing (WES) and first-generation sequencing technologies, was employed to ascertain the etiology of the disease in the child.

Identification and analysis of biomarkers associated with oxidative stress and ferroptosis in recurrent miscarriage.

Recurrent miscarriage (RM) has a huge impact on women. Both oxidative stress and ferroptosis play an important role in the pathogenesis of RM. Hence, it was vital to screen the ferroptosis oxidation-related biomarkers for the diagnosis and treatment of RM.

Identification of a Novel Homozygous Mutation in Gene Causes Very Rare Charcot-Marie-Tooth Disease Type 4B1.

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot-Marie-Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance.

Therapy management and outcome of acute hydrocephalus secondary to intraventricular hemorrhage in adults.

Background: Intraventricular hemorrhage (IVH) refers to bleeding within the brain's ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH.

Somatic mutation in intracranial extra-axial cavernous hemangiomas.

Objective: Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown.

Methods: Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort).

Endothelial hyperactivation of mutant MAP3K3 induces cerebral cavernous malformation enhanced by PIK3CA GOF mutation.

Cerebral cavernous malformations (CCMs) refer to a common vascular abnormality that affects up to 0.5% of the population. A somatic gain-of-function mutation in MAP3K3 (p.

Exosomal miR-3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations.

Aims: To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence.

Methods: Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRAS , KRAS , or KRAS lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRAS -transfected HUVECs and bAVM endothelial cells (ECs) were explored.

Novel compound heterozygous mutations of MTHFR Gene in a Chinese family with homocystinuria due to MTHFR deficiency.

Background: Homocystinuria due to methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. The purpose of this study is to expand the mutation site of the MTHFR gene and provide genetic counseling for this family.

Methods: A couple came to our hospital for pre-pregnancy genetic counseling.

KRAS mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-β/BMP-SMAD4 pathway.

Objective: Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (bAVMs), and subsequent in vivo experiments have confirmed that KRAS mutation in endothelial cells (ECs) causes AVMs in mouse and zebrafish models. Our previous study demonstrated that the KRAS mutant independently induced the endothelial-mesenchymal transition (EndMT), which was reversed by treatment with the lipid-lowering drug lovastatin. However, the underlying mechanisms of action were unclear.

Unruptured brain arteriovenous malformations causing seizures localize to one common brain network.

Seizures are a frequent symptom of unruptured brain arteriovenous malformations (bAVMs). However, the brain regions responsible for these seizures remain unclear. To identify the brain regions causally involved in bAVM-related seizures, we retrospectively reviewed 220 patients with unruptured bAVMs.

Simplex cerebral cavernous malformations with mutation have distinct clinical characteristics.

Objectives: To investigate the clinical characteristics of cerebral cavernous malformations (CCMs) with somatic mutation.

Methods: We performed a retrospective review of our CCMs database between May 2017 and December 2019. The patients with simplex CCMs identified to harbor a or CCM gene somatic mutation were included.

Compound heterozygous variants of the SLC26A4 gene in a Chinese family with enlarged vestibular aqueducts.

Background: To investigate the genetic causes of hearing loss in patients with enlarged vestibular aqueduct (EVA), the SLC26A4-related genotypes and phenotypes were analyzed. SLC26A4 gene is closely associated with EVA and its homozygous mutations or compound heterozygous mutations may cause deafness and strongly affect quality of life.

Methods: The patients who came to our hospital for hearing test and accompanied by bilateral hearing abnormalities were collected for fifteen deafness-related gene mutations detection.

Grading scale based on arcuate fasciculus segmentation to predict postoperative language outcomes of brain arteriovenous malformations.

Objective: The long-term postoperative language outcomes for brain arteriovenous malformations (bAVMs) have not been well characterised. With fibres scattered in the Broca's, Wernicke's and Geschwind's area, the arcuate fasciculus (AF) is considered as a crucial structure of language function. This study aimed to observe the language outcomes, determine the risk factors and construct a grading system for long-term postoperative language deficits (LDs) in patients with bAVMs involving the AF (AF-bAVMs).

A Nonsense Variant of Gene Associated With Weiss-Kruszka Syndrome-Like Manifestations: A Case Study and Literature Review.

This study aims to explore the clinical characteristics and genetic basis of a patient with unilateral ptosis and unilateral hearing impairment in pedigree analysis. The clinical data of the child and his father were collected. The genomic DNA of the patient and his relatives were extracted from their peripheral blood samples and subjected to trio-whole-exome sequencing (trio-WES) and copy number variation analysis.

Radiomics Analysis for Predicting Epilepsy in Patients With Unruptured Brain Arteriovenous Malformations.

To investigate the association between radiomics features and epilepsy in patients with unruptured brain arteriovenous malformations (bAVMs) and to develop a prediction model based on radiomics features and clinical characteristics for bAVM-related epilepsy. This retrospective study enrolled 176 patients with unruptured bAVMs. After manual lesion segmentation, a total of 858 radiomics features were extracted from time-of-flight magnetic resonance angiography (TOF-MRA).

Machine Learning-Enabled Determination of Diffuseness of Brain Arteriovenous Malformations from Magnetic Resonance Angiography.

The diffuseness of brain arteriovenous malformations (bAVMs) is a significant factor in surgical outcome evaluation and hemorrhagic risk prediction. However, there are still predicaments in identifying diffuseness, such as the judging variety resulting from different experience and difficulties in quantification. The purpose of this study was to develop a machine learning (ML) model to automatically identify the diffuseness of bAVM niduses using three-dimensional (3D) time-of-flight magnetic resonance angiography (TOF-MRA) images.

Identification of a novel homozygous mutation in gene causing severe fucosidosis: A case report.

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.

[Identification and expression analysis of Macaca mulatta piwil4 gene].

To investigate the structure and expression pattern of rhesus monkey PIWIL4 protein, homologous comparison and reverse transcription PCR (RT-PCR) were carried out to identify rhesus monkey piwil4. The expression of piwil4 mRNA was tested in rhesus monkey heart, brain, colon, epididymis and testis, and the result showed that piwil4 mRNA was expressed in these rhesus monkey tissues. Bioinformatic analysis suggested that the rhesus PIWIL4 protein shared 97% identity in amino acids and the same domains such as PAZ and Piwi with the human PIWIL4 (HIWI2) protein.

Identifying mRNAs bound by human RBMY protein in the testis.

Rbmy gene encodes a germ-cell specific nuclear RNA-binding protein and is involved in spermatogenesis. To further investigate the specific events of spermatogenesis in which Rbmy plays a role, the target mRNAs of human RBMY protein were isolated and identified. Through the isolating specific nucleic acids associated with proteins (SNAAP) technique, we isolated twenty potential target genes of human RBMY protein from the human testis in the present study.