Genetic Approaches for Sex Determination of Chinese Female with Male Pseudohermaphroditism

Male pseudohermaphroditism is a rare disorders of sex development(DSD)that is manifested by a female-like appearance or incompletely differentiated external genitalia in an individual with a Y chromosome.In this paper,we report our investigation of the case of a 33-year-old Chinese female who was diagnosed with a malignant mixed germ-cell tumor of the ovary.To confirm the sex of the female,we utilized genetic approaches to detect amelogenin and Y-STR loci.Y chromosome microdeletion was performed to identify existing deletions in the AZF regions and SRY.Chromosome karyotyping and whole-exome sequencing(WES)were then applied to reveal the deletion of sex chromosome segments and pathogenic variations in DNA sequences.Using DNA-STR genotyping,we detected both AMEL-X and AMEL-Y fragments.We also found haplotype Y-STR loci and detected all alleles.Furthermore,no microdeletion was detected in the AZF regions and SRY.The chromosome karyotyping was 46,XY.WES revealed a transversion mutation of 58T→C in the androgen receptor exon 1,which could be the pathogenic variant in this case of abnormal sexual development.Sex determination in forensic DNA typing is based on the amelogenin system.It is important that forensic biologists should master various genetic approaches to overcome the issue of gender ambiguity caused by DSDs.

Development and application of hyaluronic acid in tumor targeting drug delivery

Hyaluronic acid(HA)is a natural polysaccharide that has gained much attention due to its biocompatibility,enzyme degradation capacity and active tumor targeting capacity.Its receptor,CD44,is overexpressed in many kinds of cancers and is associated with tumor progress,infiltration and metastasis.Therefore,many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting.In this review,we systemically overview the basic theory of HA,its receptor and hyaluronidase,then we categorize the studies in HA-based drug delivery systems according to the functions of HA,including tumor-targeting materials,enzyme-sensitive biodegradable modality,pHsensitive component,reduction-sensitive component,and the gel backbone.Finally,the perspective is discussed.

SCNN1B and CA12 play vital roles in occurrence of congenital bilateral absence of vas deferens(CBAVD)

Dear Editor,Congenital bilateral absence of the vas deferens(CBAVD),a complete or partial defect of the Wolffian duct derivatives,is found in>25% of men with obstructive azoospermia(OA),but the underlying pathological mechanism remains poorly understood.Previous research has shown that the most common disease associated with CBAVD is cystic fibrosis(CF),the predominant manifestations of which include progressive lung disease,pancreatic dysfunction,elevated sweat chloride electrolyte,meconium ileus,and male infertility.

Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype

Whether direct manipulation of Parkinson’s disease(PD)risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue.Here,we used an adeno-associated virus serotype 9(AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras(SNs)of two monkey groups:an old group and a middle-aged group.After the operation,the old group exhibited all the classic PD symptoms,including bradykinesia,tremor,and postural instability,accompanied by key pathological hallmarks of PD,such as severe nigral dopaminergic neuron loss(>64%)and evidentα-synuclein pathology in the gene-edited SN.In contrast,the phenotype of their middle-aged counterparts,which also showed clear PD symptoms and pathological hallmarks,were less severe.In addition to the higher final total PD scores and more severe pathological changes,the old group were also more susceptible to gene editing by showing a faster process of PD progression.These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys.Taken together,this system can effectively develop a large number of genetically-edited PD monkeys in a short time(6–10 months),and thus provides a practical transgenic monkey model for future PD studies.