Novel variants of FSIP2 and SPEF2 cause varying degrees of spermatozoa damage in MMAF patients and favorable ART outcomes.

Purpose: This study identified novel variants of the FSIP2 and SPEF2 genes in multiple morphological abnormalities of the sperm flagella (MMAF) patients and to investigate the potential effect of variations on male infertility and assisted reproductive outcomes.

Methods: Whole-exome sequencing was performed in 106 Chinese MMAF patients. The discovered variants were evaluated in silico and confirmed by Sanger sequencing.

HES1 deficiency impairs development of human intestinal mesenchyme by suppressing WNT5A expression.

Serious intestinal side-effects that target the NOTCH-HES1 pathway in human cancer differentiation therapy make it necessary to understand the pathway at the human organ level. Herein, we endogenously introduced HES1-/- mutations into human embryonic stem cells (hESCs) and differentiated them into human intestinal organoids (HIO). The HES1-/- hESCs retained ES cell properties and showed gene expression patterns similar to those of wild-type hESCs when they differentiated into definitive endoderm and hindgut.

Telomeres cooperate in zygotic genome activation by affecting / transcription.

Zygotic genome activation (ZGA) is initiated once the genome chromatin state is organized in the newly formed zygote. Telomeres are specialized chromatin structures at the ends of chromosomes and are reset during early embryogenesis, while the details and significance of telomere changes in preimplantation embryos remain unclear. We demonstrated that the telomere length was shortened in the minor ZGA stage and significantly elongated in the major ZGA stage of human and mouse embryos.

A new phosphorene allotrope: the assembly of phosphorene nanoribbons and chains.

Phosphorene allotrope monolayers such as blue and red phosphorus are being designed and synthesized to be used in the optoelectronics field due to their tunable bandgap and high mobility. Using the organic molecule self-assembly method similar to the synthesis of graphene allotropes, a novel phosphorene allotrope, P monolayer, with five-, six-, and seven-membered rings is designed through the assembly of black phosphorus chains and blue phosphorene nanoribbons. molecular dynamics, phonon dispersion, and elastic constants demonstrate the dynamic, thermal, and mechanical stability of the P monolayer.

Loss-of-function p.G970D missense mutation might cause congenital bilateral absence of the vas deferens and be associated with impaired spermatogenesis.

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA).

RNA splicing analysis contributes to reclassifying variants of uncertain significance and improves the diagnosis of monogenic disorders.

Background: Numerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable.

Objective: To assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning.

Identification of paternal germline mosaicism by MicroSeq and targeted next-generation sequencing.

Background: Prezygotic de novo mutations may be inherited from parents with germline mosaicism and are often overlooked when the resulting phenotype affects only one child. We aimed to identify paternal germline mosaicism in an index family and provide a strategy to determine germline mosaicism.'

Methods: Whole-exome sequencing was performed on an Alport syndrome-affected child.

Telomerase insufficiency induced telomere erosion accumulation in successive generations in dyskeratosis congenita family.

Background: Dyskeratosis congenita (DC) is a rare heritable bone marrow failure syndrome that is associated with telomere dysfunction, and has high genetic heterogeneity and varied features.

Objective: This study aimed to identify the underlying genetic etiology of a DC family with more severe symptoms in the younger generation and to explore the relationship between the genetic causes and the severity of DC phenotype.

Methods: Whole-exome sequencing was performed on the proband to screen the candidate causative gene.

A case of megalencephalic leukoencephalopathy with subcortical cysts type 1 was identified with a novel compound heterozygous alteration (c.135delC; c.423+2dupT) in China.

We report a compound heterozygous mutation (c.135delC; c.423+2dupT) of gene in a Chinese patient underlying infantile macrocephaly and neurological deterioration in early childhood.

[Evaluation of performance of five bioinformatics software for the prediction of missense mutations].

Objective: To study the prediction performance evaluation with five kinds of bioinformatics software (SIFT, PolyPhen2, MutationTaster, Provean, MutationAssessor).

Methods: From own database for genetic mutations collected over the past five years, Chinese literature database, Human Gene Mutation Database, and dbSNP, 121 missense mutations confirmed by functional studies, and 121 missense mutations suspected to be pathogenic by pedigree analysis were used as positive gold standard, while 242 missense mutations with minor allele frequency (MAF)>5% in dominant hereditary diseases were used as negative gold standard. The selected mutations were predicted with the five software.