Preimplantation genetic testing for inborn errors of metabolism: observations from a reproductive genetic laboratory in China.

In this study, we aimed to apply preimplantation genetic testing for monogenic disorders (PGT-M) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) to block the transmission of inborn errors of metabolism (IEMs). After the disease-causing variants were identified through genetic testing, four carrier couples having children affected with IEMs, including methylmalonic aciduria, glutaric acidemia type 1, beta-ketothiolase deficiency, and ornithine transcarbamylase deficiency, sought PGT-M. A series of PGT procedures involving intracytoplasmic sperm injection, blastocyst culture, biopsy of trophectoderm cells, and next-generation sequencing (NGS)-based MARSALA, was performed to provide comprehensive chromosome screening and variant gene analysis.

Self-delivery nanodrug to manipulate tumor microenvironment for boosting photodynamic cancer immunotherapy.

Immunotherapy has captured attention for its high clinical efficacy. However, its efficacy is limited by inadequate immune activation. Therefore, a platform to activate the immune system and amplify the host's immune response against tumors is urgently needed.

Loss-of-function mutations in IQCN cause male infertility in humans and mice owing to total fertilization failure.

Fertilization failure is a significant manifestation of unexplained male infertility. Previous work has suggested a genetic origin. In this study, we report on a man with unexplained infertility from a large consanguineous marriage family.

[Detection of pathogenic variants in four patients with globozoospermia].

Objective: To explore the genetic basis for 4 patients with globozoospermia.

Methods: Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.

Cancer-testis antigen lactate dehydrogenase C4 as a novel biomarker of male infertility and cancer.

A unique lactate dehydrogenase (LDH) isoenzyme designated as lactate dehydrogenase C4 (LDH-C4) is found in mammalian mature testis and spermatozoa. Thus far, LDH-C4 has been well studied with regard to its gene and amino acid sequences, structure, biological properties, and peptide synthesis. Accumulating evidence has shown that LDH-C4 is closely related to spermatic energy metabolism and plays a critical role in sperm motility, capacitation, and fertilization.

Premature termination codons in SMN1 leading to spinal muscular atrophy trigger nonsense-mediated mRNA decay.

Background And Aims: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by SMN1 gene mutations. About 40% of SMN1 subtle mutations produced premature termination codons (PTC). This study aims to determine the capacity of these PTCs to trigger nonsense-mediated mRNA decay (NMD) pathway.

Genetic mutation analysis of 22 patients with congenital absence of vas deferens: a single-center study†.

Congenital absence of the vas deferens (CAVD), a congenital malformation of the male reproductive system, causes obstructive azoospermia and male infertility. Currently, the cystic fibrosis transmembrane conductance regulator (CFTR) has been recognized as the main pathogenic gene in CAVD, with some other genes, such as adhesion G-protein-coupled receptor G2 (ADGRG2), solute carrier family 9 isoform 3 (SLC9A3), sodium channel epithelial 1 subunit beta (SCNN1B), and carbonic anhydrase 12 (CA12), being candidate genes in the pathogenesis of CAVD. However, the frequency and spectrum of these mutations, as well as the pathogenic mechanisms of CAVD, have not been fully investigated.

Pathogenesis of acephalic spermatozoa syndrome caused by SUN5 variant.

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS; however, its pathogenesis remains unclear.

Further identification of a 140bp sequence from amid intron 9 of human FMR1 gene as a new exon.

Background: The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive.

Biallelic mutations in DCDC2 cause neonatal sclerosing cholangitis in a Chinese family.

Background: Neonatal sclerosing cholangitis (NSC) is a severe cholestatic liver disease, which often develops into end-stage liver disease in childhood and requires liver transplantation. Mutations in CLDN1 and DCDC2 are confirmed to be the main pathogenic mechanism of NSC.

Methods: Whole exon sequencing (WES) was performed to find the possible disease-causing mutations of this family.

Splicing of exon 9a in FMR1 transcripts results in a truncated FMRP with altered subcellular distribution.

FMRP is an RNA-binding protein, loss of which causes fragile X syndrome (FXS). FMRP has several isoforms resulted from alternative splicing (AS) of fragile X mental retardation 1 (FMR1) gene, but their biological functions are still poorly understood. In the analysis of alternatively spliced FMR1 transcripts in the blood cells from a patient with FXS-like phenotypes (normal CGG repeats and no mutation in coding sequence of FMR1), we identified three novel FMR1 transcripts that include a previously unidentified microexon (46 bp), terming the exon 9a.

[Prokaryotic expression and purification of mouse recombinant myelin proteolipid protein polypeptide].

Objective To establish and optimize the prokaryotic expression method for the recombinant mouse myelin proteolipid protein (PLP, 139-208 aa) which is a critical immunogenic polypeptide of PLP. Methods The sequence coding for PLP139-208 polypeptide was cloned into pET-32a(+) vector. Afterwards, the expression vector prepared in this research was transformed into E.

Hybrid minigene splicing assay verifies the pathogenicity of a novel splice site variant in the COL1A1 gene of a chinese patient with osteogenesis imperfecta type I.

Background: Osteogenesis imperfecta (OI) is a rare genetic bone disease associated with brittle bones and fractures. Among all known types, OI type I is the most common type and characterized by increased bone fragility, low bone mass, distinctly blue-gray sclera, and susceptibility to conductive hearing loss beginning in adolescence. Mutations in genes encoding type I collagen (COL1A1 and COL1A2) contribute to the main pathogenic mechanism of OI.

[Genetic analysis of a pedigree affected with congenital high myopia caused by a novel splice site variant of COL11A1 gene].

Objective: To analyze genetic variant in a pedigree affected with congenital high myopia.

Methods: Whole exome sequencing (WES) was carried out for the proband. Suspected variation was verified with Sanger sequencing.

Small Supernumerary Ring Chromosome Derived from an Inverted Duplication of 13q11.2q14 in a Fetus with Coarctation of the Aorta.

Here, we report a molecular characterization of a small supernumerary marker chromosome (sSMC) derived from the most proximal region of 13q present in a fetus with coarctation of the aorta at ultrasound examination during prenatal diagnosis. Cultured umbilical cord blood cells showed a de novo extra ring-shaped sSMC in 76% of the cells using a standard banding technique. SNP array revealed a tetrasomy of about 28.

The clinical application of preimplantation genetic diagnosis for X-linked retinitis pigmentosa.

Objective: To investigate the usefulness of preimplantation genetic diagnosis (PGD) based on mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) for a pedigree with X-linked retinitis pigmentosa (XLRP).

Methods: One pathogenic mutation (c.494G > A) of the retinitis pigmentosa GTPase regulator (RPGR) gene was identified in a pedigree affected by XLRP.

3D-cultured adipose tissue-derived stem cells inhibit liver cancer cell migration and invasion through suppressing epithelial-mesenchymal transition.

Adipose tissue-derived stem cells (ADSCs) are considered promising candidates for stem cell therapy; however, the tumorigenicity of ADSCs remains controversial. The present study aimed to investigate the association between ADSCs and liver cancer cells, and to determine whether culture methods could influence the effects of ADSCs on liver cancer cell growth in vitro. Liver cancer cells were treated with ADSCs-conditioned medium (CM) that was collected using the two-dimensional (2D) culture method, sphere culture method, or three-dimensional (3D) culture method.

Associations of rs823128, rs1572931, and rs823156 polymorphisms with reduced Parkinson's disease risks.

The PARK16 locus is considered to play a protective role in Parkinson's disease (PD). However, the epidemiological evidence on the relationships between PARK16 single-nucleotide polymorphisms (rs823128, rs1572931, and rs823156) and PD is inconsistent. Therefore, we carried out a meta-analysis to validate the relationships and performed a bioinformatic analysis to explore putative regulation mechanisms of the single-nucleotide polymorphisms in PD.

[Phenotypic and genetic analysis of an inv dup(15) case with a BP3:BP3 rearrangement].

Objective: To analyze a case of supernumerary marker chromosome (SMC) with combined genetic techniques and explore its correlation with the clinical phenotype.

Methods: The SMC was analyzed with G-banded karyotyping, multiplex ligation dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP-array).

Results: G-banding analysis indicated that the patient has a karyotype of 47,XX,+mar.

Single Nucleotide Polymorphism of the Enhancer of Zeste Homolog 2 Gene rs2072408 is Associated with Lymph Node Metastasis and Depth of Primary Tumor Invasion in Gastric Cancer.

Background: The single nucleotide polymorphism (SNP) rs2072408 is located in an intron of the enhancer of zeste homolog 2 (EZH2) gene. Its role in gastric cancer (GC) has not been determined.

Methods: In the present study, the genotype of (EZH2) rs2072408 and the relationship of genotype with lymph node metastasis (LNM) and the invasive depth of gastric wall (T stage) was determined in 330 patients with GC, and the association between the genotype and recurrence and survival was determined in 253 patients with GC.

A new bioinformatic insight into the associated proteins in psychiatric disorders.

Background: Psychiatric diseases severely affect the quality of patients' lives and bring huge economic pressure to their families. Also, the great phenotypic variability among these patients makes it difficult to investigate the pathogenesis. Nowadays, bioinformatics is hopeful to be used as an effective tool for the diagnosis of psychiatric disorders, which can identify sensitive biomarkers and explore associated signaling pathways.

[Construction and application of eukaryotic expression vector of fragile X mental retardation 1 (FMR1) gene].

Objective To construct a eukaryotic expression vector of human fragile X mental retardation 1 (FMR1) gene and establish stably transfected HeLa cells. Methods The full-length FMR1 cDNA fragment was amplified by PCR and inserted into eukaryotic expression vector pEGFP-N2 using restriction enzyme. The recombinant plasmid pEGFP-N2-FMR1, after identified by restriction digestion and DNA sequencing, was transfected into HeLa cells by lipofectamine 2000.

Bioinformatics analysis of gene expression profiles of dermatomyositis.

Dermatomyositis (DM) is a type of autoimmune inflammatory myopathy, which primarily affects the skin and muscle. The underlying mechanisms of DM remain poorly understood. The present study aimed to explore gene expression profile alterations, investigate the underlying mechanisms, and identify novel targets for DM.