Identification of a novel missense NIPBL variant in a juvenile with severe type of Cornelia de Lange syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS).@*METHODS@#A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis.@*RESULTS@#A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin_N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein.@*CONCLUSION@#The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.

Identification of a novel de novo variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS).@*METHODS@#The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis.@*RESULTS@#A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function.@*CONCLUSION@#The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.

The effect of chronic hypoxia on expression of oncogene erbB in rat lung / 中国病理生理杂志

In order to assess whether there is any abnormality in oncogene expression in hypoxia induced pulmonary hypertension, the expression of oncogene erbB in the lung tissue of rats with and without hypoxia was detected by in situ hybridization with digoxingenin as a prob label. The results showed that there was a slight expression of erbB mRNA in control normoxic rats. After hypoxia for 7 to 21 days, its expression increased significantly as compared with that in control (P