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Objective: To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD)., Methods: Two children with HMGCLD diagnosed at Henan Provincial Children's Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively., Results: Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutaconic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c.722C>T variants of the HMGCL gene, which was rated as uncertain significance (PM2_Supporting+PP3). Child 2 was found to harbor homozygous c.121C>T variants of the HMGCL gene, which was rated as pathogenic variant (PVS1+PM2_Supporting+PP4)., Conclusion: Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.

: To analyze the clinical and genetic characteristics of children with Keishi-Bukuryo-Gan (KBG) syndrome. The clinical and genetic data of 5 children with KBG syndrome admitted in Children's Hospital Affiliated of Zhengzhou University from November 2018 to September 2020 were retrospectively analyzed. Five children were all males who came from four different families. All children presented triangular face, bushy eyebrows, thin upper lip, large or delayed closure of anterior fontanel, and abnormal bone development. Four cases had growth retardation, large ears, thick ear lips; 3 cases had large central incisors; 2 cases had congenital heart disease; 2 cases had abnormal skin changes; 2 cases had genital changes; and 2 cases became grumpy. Liver and kidney function,thyroid function, blood gas analysis and electrolyte of the children were all in the normal range. Three children received bone age examination, and all showed bone age lag. Two cases showed backward myelination of white matter in MRI. Whole exome sequencing revealed that all 5 children had heterozygous mutations in the gene, among which c.6836_6837delTG, c.5866C>T, and c.6270delT were newly discovered mutation sites. None of the parents of probands were found to carry the mutations in gene. Two cases achieved height catch-up and cognitive improvement after treatment with recombinant human growth hormone. KBG syndrome is characterized by a wide spectrum of phenotypes, and large or delayed closure of the anterior fontanel, large ears and thick ear lips may be the main manifestations of the disease in infants and young children. gene mostly presents spontaneous mutations, and early application of growth hormone therapy can achieve height catch-up and cognitive improvement without obvious adverse reactions.

Objective: To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature., Methods: Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software., Results: The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4)., Conclusion: The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.

Objective: To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity., Methods: Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results., Results: NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation., Conclusion: A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.

Pituitary adenomas, arising from the pituitary gland cells, are one of the most frequent tumors found in the sella region. However, the molecular mechanisms involved in the carcinogenesis and progression of pituitary adenomas is still not understood in detail. Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2), a newly identified lncRNA, has been reported to be abnormally expressed in some cancers. In the present study, we found that CCAT2 was significantly upregulated in pituitary adenomas tissues. Elevated CCAT2 expression was correlated with poor prognosis in patients with pituitary adenomas. Moreover, CCAT2 expression was activated by E2F1. Loss-of-function and gain-of-function assays showed that CCAT2 positively regulated pituitary adenoma cell proliferation, migration, and invasion. Further investigation demonstrated that CCAT2 interacted with PTTG1, and promoted its stability. Furthermore, CCAT2 affected the expression of downstream genes regulated by PTTG1, including SOX2 , DLK1 , MMP2 , and MMP13 . Cumulatively, CCAT2 functions as an oncogene in pituitary adenomas and its overexpression contributes to pituitary adenoma carcinogenesis and progression., Competing Interests: None.