Creatine Kinase-MM/Proto-oncogene Tyrosine-Protein Kinase Receptor as a Sensitive Indicator for Duchenne Muscular Dystrophy Carriers.

Duchenne muscular dystrophy (DMD), a lethal X-linked recessive genetic disease, is characterized by progressive muscle wasting which will lead to premature death by cardiorespiratory complications in their late twenties. And 2.5-19% DMD carriers that also suffer from skeletal muscle damage or dilated cardiomyopathy when diagnosed as soon as possible is meaningful for prenatal diagnosis and advance warning for self-health.

A high-throughput luciferase reporter assay for screening potential gasdermin E activators against pancreatic cancer.

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC.

Evaluating the performance of four assays for carrier screening of spinal muscular atrophy.

Background And Aims: Spinal muscular atrophy (SMA) is an autosomal recessive inherited neuromuscular condition caused by biallelic mutations in the survival of motor neuron 1 (SMN1) gene. A homozygous deletion of the SMN1 gene accounts for approximately 95-98% of SMA patients. A highly homologous gene survival motor neuron 2 (SMN2) can partially compensate for SMN1 deletion, and its copy number is associated with disease severity.

Identification of two novel DNAJC12 gene variants in a patient with mild hyperphenylalaninemia.

Background: Recently, variants in DNAJC12 were reported to be a novel genetic cause of hyperphenylalaninemia (HPA); however, thus far, fewer than fifty cases have been reported worldwide. Some patients with DNAJC12 deficiency present with mild HPA, developmental delay, dystonia, Parkinson's disease and psychiatric abnormalities.

Methods: Herein, we report the case of a two-month-old Chinese infant with mild HPA, detected by newborn screening.

[Clinical features and genetic variants of a case with carnitine palmitoyltransferase 1A deficiency].

Objective: To identify the possible pathogenesis of a neonate with carnitine palmitoyltransferase 1A (CPT1A) deficiency by analyzing gene variants.

Methods: Potential variants were detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases, and gene variants were verified by Sanger sequencing.

Results: Genetic testing indicated that the neonate has carried c.

[Tandem mass spectrometry and genetic variant analysis of four neonates with very long chain acyl-coenzyme A dehydrogenase deficiency].

Objective: To analyze the clinical features and genetic variants in four neonates with very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency.

Methods: Neonates with a tetradecenoylcarnitine (C14:1) concentration at above 0.4 μmol/L in newborn screening were recalled for re-testing.

Retrospective analysis of isobutyryl CoA dehydrogenase deficiency.

Background: Isobutyryl-CoA dehydrogenase deficiency is a rare, autosomal recessive hereditary disease caused by a disorder in valine metabolism due to the deficiency of isobutyryl-CoA dehydrogenase. We provided two new mutations for ACAD8 and analyzed new sight to explore the association between the clinical phenotype and genotype of this disease.

Methods: The concentration of butyrylcarnitine was tested by tandem mass spectrometry.

A joint method for the screening of pharmacological chaperones for phenylalanine hydroxylase.

Phenylalanine hydroxylase (PAH) deficiency (PAHD) is an autosomal recessive disorder that causes severe injury to the nervous system, the treatment of which mainly depends on dietary therapy. The limited treatment options for PAHD are an incentive to develop new methods to identify more efficient therapeutic drugs, such as agonists which could improve PAH activity. In this study, we aimed to establish a rapid and convenient method for the screening and verification of PAH agonists.

Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population.

Background: Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates.

Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life.

Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis.

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3.

A novel COQ8A missense variant associated with a mild form of primary coenzyme Q10 deficiency type 4.

Background: Primary coenzyme Q10 deficiency refers to a group of diseases characterised by reduced levels of coenzyme Q10 in related tissues or cultured cells associated with the 9 genes involved in the biosynthesis of coenzyme Q10. A biallelic pathogenic variant of COQ8A gene causes the occurrence of the primary coenzyme Q10 deficiency type 4. The objective of this study was to investigate the genetic cause of muscle weakness in a proband who had a negative DMD gene test for Becker muscular dystrophy.

Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women.

Spinal muscular atrophy (SMA) is a relatively common, life-shortening, autosomal recessive neuromuscular disease. The carrier frequency of SMA ranges from approximately 0.98% to 2.

Analysis of five cases of hypermethioninemia diagnosed by neonatal screening.

Background Hypermethioninemia is a group of diseases with elevated plasma methionine (Met) caused by hereditary and non-hereditary factors, although it could also be caused by administration of the amino acid Met. Among these, the disease caused by methionine adenosyltransferase (MAT) I/III deficiency is the most common, and is characterized by persistent, isolated hypermethioninemia as well as slightly elevated homocysteine. S-adenosylmethionine is the product of Met, which can be used as a direct methyl donor of many substances, such as choline and nucleotide, and essential in the development of the body.

[Analysis of AGR1 gene variants in an infant with early-onset argininemia].

Objective: To explore the genetic basis for an infant with early-onset argininemia.

Methods: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing.

A novel splice site mutation in the UBE2A gene leads to aberrant mRNA splicing in a Chinese patient with X-linked intellectual disability type Nascimento.

Background: X-linked intellectual disability type Nascimento (XIDTN), caused by mutations in ubiquitin-conjugating enzyme E2A (UBE2A) gene, is characterized by moderate to severe intellectual disability, impaired speech, urogenital anomalies, skin abnormalities, and dysmorphic facial features.

Methods: Whole-exome sequence was carried out in the patients, and the variant of disease-associated gene in the patient and his parents was confirmed by Sanger sequencing. RNA transcript analysis by reverse transcription (RT)-PCR was performed to assess the potential effects of the splice site mutation.

[Clinical and genetic analysis of two children suspected for argininosuccinic aciduria].

Objective: To analyze the clinical and genetic features of two children suspected for arginylsuccinuria aciduria.

Methods: The patients were subjected to high-throughput sequencing using a gene panel.

Results: Both patients had high citrulline (87.

A method using angiotensin converting enzyme immobilized on magnetic beads for inhibitor screening.

Angiotensin converting enzyme (ACE), fusing with FLAG tag, was overexpressed in human embryonic kidney 293T cells. This recombinant FLAG-tagged ACE was immobilized on anti-FLAG antibody coated magnetic beads by affinity method in crude cell lysate for the first time. The enzyme-immobilized magnetic beads (ACE-MB), without further cleavage procedure, were used directly to establish a cost-effective and reliable method for screening ACE inhibitors by coupling with fluorescence detection.