Hypoglycemia is unusual in patients carrying POU1F1 gene variants and requires close attention in clinical practice. For children with multiple pituitary hormone deficiency, genetic testing should be recommended to determine the cause.

To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid (3-MGA) through sequencing of the CLPB gene.

Genomic DNA of the infant was sequenced by next generation sequencing (NGS), and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis.

NGS has revealed that the infant has carried a c.1085G>A (p.Arg362Gln) and a c.1700A>C (p.Tyr567Ser) of the CLPB gene, which were respectively inherited from her parents. Among these, c.1085G>A (p.Arg362Gln) is a novel variant which was unreported previously, and based on the ACMG guidelines, it was predicted to be a possible pathogenic variant.

Compound heterozygous variants c.1085G>A (p.Arg362Gln) and c.1700A>C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.

C (p.Tyr567Ser) of the CLPB gene probably underlay the disease in this infant. Genetic testing has confirmed the diagnosis.

To analyze the clinical and molecular characteristics of a child with very long chain acyl-CoA dehydrogenase deficiency (VLCADD).

Peripheral blood sample of the patient was collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out for the proband. Suspected mutations were validated by Sanger sequencing.

The patient, a 12-month-old girl, was admitted for diarrhea, vomiting, fever, poor spirit and decreased blood pressure. During the course of the disease, she also manifested hypertrophic cardiomyopathy, cardiogenic shock, elevated myocardial enzyme kinase, fever and metabolic acidosis, and had died after three days due to ventricular tachycardia and respiratory failure. Genetic testing showed that she has carried heterozygous mutations of of the ACADVL gene, namely c.664G>A (exon 8) and c.1056_1057del (exon 10). Blood screening for metabolic genetic diseases showed increased C12, C14, C16, C18, C141, C142, C161, C4/C3 and C8/C3, accompanied with decreased C0, C0/C16 and C8/C10. VLCADD and secondary carnitine deficiency could not be excluded, which was in keeping with the result of genetic testing.

The child was diagnosed with VLCADD, which may be attributed to the compound heterozygous c.664G>A and c.1056_1057del variants of the ACADVL gene.

A and c.1056_1057del variants of the ACADVL gene.

To explore the clinical features and molecular basis of a Chinese pedigree with two siblings affected by cytochrome P450 oxidoreductase deficiency (PORD).

Clinical features of the patients were reviewed, and their genomic DNA was subjected to next generation sequencing (NGS).

The two siblings presented peculiar facies, genital hypoplasia and skeletal deformity. NGS revealed that both have carried compound heterozygous variants of the POR gene, namely c.1370G>A and c.517-19_517-10delGGCCCCTGTGinsC, which were respectively inherited from their parents.

Both siblings were diagnosed with PORD based on sequencing of the POR gene. The newly discovered POR c.517-19_517-10delGGCCCCTGTGinsC has enriched the spectrum of PORD-related genetic variants.

Both siblings were diagnosed with PORD based on sequencing of the POR gene. The newly discovered POR c.517-19_517-10delGGCCCCTGTGinsC has enriched the spectrum of PORD-related genetic variants.

To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2 (CCDS2).

Clinical data of the child was collected. Whole-exome sequencing was carried out to identify potential variants by next generation sequencing. Candidate variants were confirmed by Sanger sequencing. Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy. Treatment was carried out following the diagnosis and genetic counseling for the affected family.

Two novel heterozygous variants (c.289delC and c.392-1G>C) of the GAMT gene were identified in the proband, which were respectively inherited from her father and mother. In silico analysis suggested both variants to be pathogenic. Creatine (Cr) level of the child was very low, and cerebral guanidinoacetate (GAA) level was slightly increased. But both had recovered to normal in two weeks, and cerebral Cr level was significantly improved after two months. Intellectual and motor development of the child were significantly improved.

The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.

The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.

To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency.

The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members.

Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant.

Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. this website Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.

To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock

variant mice modeling bipolar disorder manic disorder.

Open field test and Elevated plus-maze test were carried out on the Clock

mutant and wild-type control groups. The frontal lobe and hippocampus of Clock

mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0.

The Clock

mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock

mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes.