Identification of novel COL4A5 variants and prenatal diagnosis in three large families.

Alport syndrome (AS) is the second-most frequent monogenic kidney disease and 85% of cases are caused by mutations in the genes of the α5 chains of collagen type IV (COL4A5). The early diagnosis and treatment are essential for the prognosis of AS. The clinical phenotypes of AS are very variable, which is challenging to diagnose.

Mate-pair sequencing assisted prenatal counseling for a rare complex chromosomal rearrangement carrier.

Objective: This study was aimed to identify a rare complex rearrangement and assist prenatal counseling.

Method: Mate-pair sequencing (MPseq) combined with karyotypes, copy number variants sequencing and whole exome sequencing was used to provide accurate chromosome breakpoints and assist prenatal diagnosis for a mentally retarded pregnant woman.

Result: MPseq indicated a complex rearrangement involved 25 breakpoints and fusions, disrupting 6 genes.

Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

Purpose: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them.

Methods: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant.

Identification of two novel and one rare mutation in and prenatal diagnoses in three Chinese families with intellectual Disability-7.

Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, and febrile seizures at an age of early onset, then progressive intellectual and physical development deterioration. We purposed to identify the underlying causative genetic factors of three individuals in each Chinese family who presented with symptoms of intellectual disability and facial dysmorphic features. We provided prenatal diagnosis for the three families and genetic counseling for the prevention of this disease.

Identification of five novel variants.

Background: Epilepsy is characterized by recurrent unprovoked seizures. Mutations in the voltage-gated sodium channel alpha subunit 1 () gene are the main monogenic cause of epilepsy. Type and location of variants make a huge difference in the severity of disorder, ranging from the mild phenotype (genetic epilepsy with febrile seizures plus, GEFS+) to the severe phenotype (developmental and epileptic encephalopathies, DEEs).

Screening and mutation analysis of phenylalanine hydroxylase deficiency in newborns from Jiangxi province.

Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase () gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time.

Mutation spectrum of gene in patients with tetrahydrobiopterin deficiency from jiangxi province.

Hyperphenylalaninemia (HPA) is the most common inborn error in amino acid metabolism. It can be primarily classified into phenylalanine hydroxylase (PAH) deficiency and tetrahydrobiopterin (BH4) deficiency. BH4 deficiency (BH4D) is caused by genetic defects in enzymes involved in the biosynthesis and regeneration of BH4.

Damaged DNA Is an Early Event of Neurodegeneration in Induced Pluripotent Stem Cell-Derived Motoneurons with UBQLN2 Mutation.

(UBQLN2) mutations lead to familial amyotrophic lateral sclerosis (FALS)/and frontotemporal dementia (FTLD) through unknown mechanisms. The combination of iPSC technology and CRISPR-mediated genome editing technology can generate an iPSC-derived motor neuron (iPSC-MN) model with disease-relevant mutations, which results in increased opportunities for disease mechanism research and drug screening. In this study, we introduced a UBQLN2-P497H mutation into a healthy control iPSC line using CRISPR/Cas9, and differentiated into MNs to study the pathology of UBQLN2-related ALS.

Full-Length Dystrophin Restoration via Targeted Exon Addition in DMD-Patient Specific iPSCs and Cardiomyocytes.

Duchenne muscular dystrophy (DMD) is the most common fatal muscle disease, with an estimated incidence of 1/3500-1/5000 male births, and it is associated with mutations in the X-linked gene encoding dystrophin, the largest known human gene. There is currently no cure for DMD. The large size of the gene hampers exogenous gene addition and delivery.

An Episomal CRISPR/Cas12a System for Mediating Efficient Gene Editing.

(1) Background: Gene editing technology, as represented by CRISPR is a powerful tool used in biomedical science. However, the editing efficiency of such technologies, especially in induced pluripotent stem cells (iPSCs) and other types of stem cells, is low which hinders its application in regenerative medicine; (2) Methods: A gene-editing system, COE, was designed and constructed based on CRISPR/Cas12a and Orip/EBNA1, and its editing efficiency was evaluated in human embryonic kidney 293T (HEK-293T) cells with flow cytometry and restriction fragment length polymorphism (RFLP) analysis. The COE was nucleofected into iPSCs, then, the editing efficiency was verified by a polymerase chain reaction and Sanger sequencing; (3) Results: With the extension of time, COE enables the generation of up to 90% insertion or deletion rates in HEK-293T cells.

Targeted addition of mini-dystrophin into rDNA locus of Duchenne muscular dystrophy patient-derived iPSCs.

Duchenne muscular dystrophy (DMD), the most common lethal muscular disorder, affects 1 in 5000 male births. It is caused by mutations in the X-linked dystrophin gene (DMD), and there is no effective treatment currently. Gene addition is a promising strategy owing to its universality for patients with all gene mutations types.

Mesenchymal stem cells derived from iPSCs expressing interleukin-24 inhibit the growth of melanoma in the tumor-bearing mouse model.

Background: Interleukin-24 (-) is a therapeutic gene for melanoma, which can induce melanoma cell apoptosis. Mesenchymal stem cells (MSCs) show promise as a carrier to delivery anti-cancer factors to tumor tissues. Induced pluripotent stem cells (iPSCs) are an alternative source of mesenchymal stem cells (MSCs).

Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells.

Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by progressive motor neuron loss in the spinal cord. It is caused by mutations in the survival motor neuron 1 (SMN1) gene. SMN1 has a paralogous gene, survival motor neuron 2 (SMN2), in humans that is present in almost all SMA patients.