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Background: Epilepsy in childhood is a common and diverse neurological disorder. We conducted a genetic and phenotype analysis of a Chinese cohort of infants and children with epilepsy.Methods: We conducted a pedigree analysis of 260 Chinese patients with epilepsy onset during infancy or childhood by whole exome sequencing (WES).Results: Of the 260 probands analyzed, a genetic diagnosis was established in 135 patients. One-hundred eighty-eight phenotypes were detected in those 135 positive/likely positive patients, 106 patients had more than two phenotypes, and 67 patients had more than three phenotypes. A total of 142 variants of 81 genes were detected among the positive/likely positive patients. Among these 142 variants, of which 87 of 66 genes were novel.Conclusion: Our findings extend the variant spectrum of genes related to epilepsy. Our results will be useful for genetic testing and counseling for patients with epilepsy.

Summary: Long‐term repopulating haematopoietic stem cells (LT‐HSCs) have the ability to reconstitute the entire haematopoietic system following transplantation permanently. Despite great achievements in HSC transplantation, the limited transplantable HSC number, especially LT‐HSCs, remains critical for successful transplantation and broader applications. In this study, we established a defined serum‐free culture system for in vitro expansion of LT‐HSCs. This culture system (E1) expanded LT‐HSCs from umbilical cord blood, human mobilization peripheral blood and bone marrow. These E1‐expanded HSCs reconstituted the haematopoietic and immune systems in primary and secondary transplanted mice in a short time. Better haematopoietic reconstitution was observed in secondary xenografted mice. Moreover, we obtained the comprehensive expression profile and cellular components of LT‐HSCs from umbilical cord blood. Our study provides a valuable tool for LT‐HSC research and may improve clinical applications of HSCs. [ABSTRACT FROM AUTHOR]

Background: Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain‐hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available. Methods: In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral‐facial‐digital defects and was therefore classified as an oral‐facial‐digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings. Results: Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C>T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in CPLANE1 (NM_023073.3). Conclusion: This study reports that two novel CPLANE1 variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with CPLANE1 variants. [ABSTRACT FROM AUTHOR]

Advances in third-generation sequencing technologies provide an opportunity to investigate the complex organizational structure of the genome and unravel the genetic mechanisms of disease and physiological traits. Here we report the sequencing and de novo assembly of a healthy male northern Han Chinese genome and detection of structural variants using only nanopore sequencing data. We performed de novo assembly after filtering the raw data. Then, we aligned the assembled contigs to the human reference genome, and visualized chromosomes plot, which illustrated the contiguity of the nanopore assembly. Additionally, genomic structural variants were detected using a structure variation detection tool with long-read sequencing data. Median coverage depth was 30-fold and the read N50 was 27,136 bp. 96.51% of reads had at least one alignment to the human reference genome. The final assembled genome was 2.85 GB in size, with an N50 contig size of 5.4 MB. We identified 20,085 structural variants. Third-generation sequencing technologies have many advantages in de novo whole-genome assembly and detection of structural variants. Our results provide reference data for disease research, and can be used as a novel population-specific dataset of structural variants to support the efficient development of personalized precision medicine. [ABSTRACT FROM AUTHOR]

Background: Joubert syndrome (JS, OMIM: 213300) is a recessive developmental disorder characterized by cerebellar vermis hypoplasia and a distinctive mid‐hindbrain malformation called the "molar tooth sign" on axial magnetic resonance imaging. To date, more than 35 ciliary genes have been identified as the causative genes of JS. Methods: Whole exome sequencing was performed to detect the causative gene mutations in a Chinese patient with JS followed by Sanger sequencing. RT‐PCR and Sanger sequencing were used to confirm the abnormal transcript of centrosomal protein 104 (CEP104, OMIM: 616690). Results: We identified two novel heterozygous mutations of CEP104 in the proband, which were c.2364+1G>A and c.414delC (p.Asn138Lysfs*11) (GenBank: NM_014704.3) and consistent with the autosomal recessive inheritance mode. Conclusion: Our study reported the fourth case of JS patients with CEP104 mutations, which expands the mutation spectrum of CEP104 and elucidates the clinical heterogeneity of JS. [ABSTRACT FROM AUTHOR]