Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (types 1-4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase chain reaction and repeat-primed polymerase chain reaction, we identified an intronic pentanucleotide (TTTCA)n insertion in the SAMD12 gene as the cause, which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional seven unmapped pedigrees. Only two pedigrees did not contain the (TTTCA)n insertion. Repeat-primed polymerase chain reaction revealed that the sizes of (TTTCA)n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion (ATTTCATTTC)58 has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.

This study investigated the protective effects of sodium alginate (SA) on the gut microbiota, immunity, and intestinal mucosal barrier function in cyclophosphamide-induced immunosuppressed BALB/c mice. SA alleviated spleen tissue damage and restored impaired immune functions, such as increasing the immune organ index, decreasing splenic T lymphocytes, and markedly increasing the secretion of serum immunoglobulins and cytokines in immunosuppressed mice. In addition, SA reversed the intestinal mucosal injury and increased the intestinal permeability by upregulating the expression of tight junction proteins. Moreover, SA decreased gut inflammation by reducing serum D-lactic acid (D-LA) and lipopolysaccharide (LPS) concentrations and downregulating toll-like receptor 4 (Tlr4) and mitogen-activated protein kinase (Mapk) pathway expression. Furthermore, SA significantly increased the abundance of beneficial bacteria (Lactobacillus, Roseburia, and Lachnospiraceae NK4A136) and decreased pathogenic bacteria (Helicobacter, Peptococcus, and Tyzzerella) in the intestine as determined by 16S rRNA gene high-throughput sequencing. In conclusion, our study provides a scientific basis for SA as a functional food in modulating gut microbiota and protecting against intestinal mucosal injury and indicates that SA has potential application for enhancing immunity.

We provided the clinical and neurophysiological features of familial cortical myoclonic tremor with epilepsy patients. This study is reported for the presentation of this rare disease in a Chinese population with the largest single report on familial cortical myoclonic tremor with epilepsy worldwide. Age-at-onset anticipation of cortical tremor with paternal transmission was statistically significant, which further confirmed a possibility of unstable expanding repeat in the genetic mechanism of familial cortical myoclonic tremor with epilepsy. © 2016 International Parkinson and Movement Disorder Society.

BackgroundIntronic pentanucleotide insertion in the sterile alpha motif domain‐containing 12 gene was recently identified as the genetic cause of familial cortical myoclonic tremor with epilepsy type 1.ObjectivesWe thereafter conducted a multimodal MRI research to further understand familial cortical myoclonic tremor with epilepsy type 1.MethodsWe enrolled 31 patients carrying heterozygous pathogenic intronic pentanucleotide insertion in the sterile alpha motif domain‐containing 12 gene and 31 age‐ and sex‐matched healthy controls. We compared multimodal MRI metrics, including voxel‐based morphometry, fractional anisotropy of diffuse tensor imaging, frequency‐dependent percent amplitude fluctuation, and seed‐based functional connectivity of resting‐state functional MRI.ResultsSignificant decreased gray matter volume was found in the cerebellum. Percent amplitude fluctuation analysis showed significant interaction effect of “Frequency by Group” in three regions, including the vermis VIII, left cerebellar lobule VIII, and left precentral gyrus. Specifically, the lowest‐frequency band exhibited significant increased percent amplitude fluctuation in patients in the two cerebellar subregions, whereas the highest‐frequency band exhibited decreased percent amplitude fluctuation in the precentral gyrus in patients. Discriminative analysis by support vector machine showed a mean accuracy of 82% (P = 1.0–5). An increased functional connectivity between vermis VIII and the left precentral gyrus was found in patients with familial cortical myoclonic tremor with epilepsy type 1. A positive correlation between the percent amplitude fluctuation in the left cerebellar lobule VIII and duration of cortical tremor was also found.ConclusionThe cerebellum showed both structural and functional damages. The distinct change of spontaneous brain activity, that is, increased ultra‐low‐frequency amplitude in the cerebellum and the decreased higher‐frequency amplitude in the motor cortex, might be a pathophysiological feature of familial cortical myoclonic tremor with epilepsy type 1. © 2020 International Parkinson and Movement Disorder Society

Rationale:Retroperitoneal bronchogenic cysts without specific clinical manifestations are extremely rare and difficult to diagnose preoperatively and are easily misdiagnosed as left adrenal or pancreatic tumors.Patient concerns:A 48-year-old woman with the chief complaint of obscure epigastric pain for 1 month and with no other gastrointestinal symptoms and no significant medical history. The patient had signed informed consent for publication of this case report.Diagnosis:The serum level of carbohydrate antigen 19-9 (CA 19-9) in the patient was >1200 U/mL, which far exceeded the normal level of <37 U/mL. Computed tomography (CT) initially suggested the presence of an adrenal tumor. However, endoscopic ultrasound (EUS) showed that the adrenal gland had an intact capsule and that the mass originated in the retroperitoneal space and did not involve the paranephros.Interventions:Surgical resection was performed on the patient.Outcomes:Histopathological examination demonstrated that the mass was a retroperitoneal bronchogenic cyst. At the 2-month postoperative follow-up, the level of CA 19-9 had returned to normal.Lessons:EUS appears to be superior to CT because it clearly delineated the mass from the surrounding structures of the retroperitoneal region. EUS-fine needle aspiration can be used for diagnosis or determining whether the mass is malignant or benign. To the best of our knowledge, retroperitoneal bronchogenic cysts with significantly elevated serum CA 19-9 have not been reported. Measurement of serum CA 19-9 may be helpful in the diagnosis of retroperitoneal bronchogenic cysts. However, this was a rare case, and the mechanism behind CA 19-9 elevation is not clear and needs further investigation.