OBJECTIVETo explore the clinical value of the neonatal hearing combined with deafness gene screening.METHODSFrom February 2014 to August 2015, 1933 newborns were included in the study. We analyzed the effects of combined screening of hearing and deafness gene.RESULTSAmong all the 1933 neonates, 71.34% (1379/1933) passed and 28.66% (554/1933) failed the initial hearing screening.The hearing impairment rate was 4.14‰ (8/1933). Genetic screening mutation rate was counted. GJB2 mutation rate was 28.97‰ (56/1933). SLC26A4 mutation rate was 13.97‰ (27/1933). GJB3 mutation rate was 6.21‰ (12/1933). Mitochondrial 12 S rRNA gene mutation rate was 1.03‰ (2/1933). 1 case of 235 delc homozygous mutation did not pass the initial hearing screening and lost to follow-up rescreening. 2 cases of 12 S rRNA 1555A>G homogeneous mutations passed early hearing screening. 8 cases of auditory handicaps were all normal.CONCLUSIONDeafness gene screening can make up for the deficiencies of the universal newborn hearing screening. Joint use of both of them should complement each other and play the biggest role.

Objective To explore the changes of plasma melatonin(MT)level in hypoxic-ischemic encephalopathy(HIE)neonates,and elucidate the function of rnelatonin in the pathogenesis and the prognosis of HIE.Methods Fourty HIE neonates were divided into 2 groups,20 mild HIE neonates and 20 moderate or severe HIE ones.The femoral vein blood were collected in 48 h and on 7 d after birth in mild HIE group,and in 48 h,on 7 d and(14±4)d after birth in moderate on severe HIE group.Twenty normal term infants served as control group.The level of plasma MT was determined with enzyme-labeled immunosorbent assay.Results Compared with control group[(8.003±1.840)ng/L],The MT level in mild HIE group in 48 h after birth[(13.311±4.025)ng/L]was higher(P＜0.01),but there was no difference on 7 d[(6.605±1.269)ng/L](P＞0.05);The MT level in moderate or severe HIE group in 48 h after birth[(5.487±1.997)ng/L]was lower(P＜0.01),but it was higher on 7 d[(16.201±5.594)ng/L](P＜0.01),there was no difference on(14±4)d[(6.799±1.765)ng/L](P＞0.05).Conclusion MT may have protective action on HIE.The prognosis of HIE with rising MT level in 48 h after birth is better than that with lower MT level.

OBJECTIVETo explore the effect of recombinant human soluble CD(40) ligand (rhsCD(40)L) and CD(40)L cDNA transfected cell (CD(40)L-TC) on the behavior of malignant B lymphocytes, and investigate the possibility of using rhsCD(40)L as a new bio-factor in tumor immunotherapy.

METHODrhsCD(40)L and CD(40)L-TC were obtained by gene recombinant techniques. Multiple myeloma cell lines, XG2, XG7, U266 and 8226, B-lymphoma cell lines, Raji and Daudi were selected to detect responses to rhsCD(40)L and CD(40)L-TC stimulation. Cell growth curve, cell cycle, early apoptosis as well as membrane surface molecules on these cell lines were analyzed.

RESULTS(1) The expression levels of CD(40) molecule on malignant B lymphocytes showed heterogeneity. High level of CD(40) on XG2, moderate on 8266, Raji, and Daudi, and no expression on U266 and XG7 were detected. The rhsCD(40)L stimulation gave rise to a typical homo-type cell aggregation of XG2 and Daudi. Meanwhile, at least 10 to 20 of CD(40)(+) XG2 or CD(40)(+) Daudi cells were found adherent to one pre-treat ed CD(40)L-TC. (2) Co-incubation with rhsCD(40)L (5 micro g/ml), or CD(40)L-TC (tumor cell: CD(40) = 5:1) resulted in a significant inhibition of in vitro cell growth of XG2, Raji and Daudi, with G(1)-phase arrest for XG2 and G(2)-phase for Raji and Daudi. These two kinds of CD(40) stimulators induced XG2, Raji and Daudi cells to apoptosis in vitro. The apoptotic rate for XG2 was 23.3% (rhsCD(40)L) and 18.8% (CD(40)L-TC), for Daudi 14.2% and 15.9%, and for Raji 11.6% and 8.9% respectively. (3) Phenotype analysis showed that CD(95) expression levels were significantly up-regulated on XG2, Raji and Daudi after stimulation with rhsCD(40)L or CD(40)L-TC, and CD(80) and CD(18) expression levels on Raji were respectively enhanced and decreased.

CONCLUSIONThe abilities to directly inhibit XG2, Daudi and Raji cell proliferation, to induce themapoptosis, as well as to up-regulate immune co-stimulator molecule CD(80) expression on Raji cells would make rhsCD(40)L a potential bio-factor for tumor immuno-therapy.

B-Lymphocytes ; drug effects ; metabolism ; pathology ; CD40 Antigens ; metabolism ; CD40 Ligand ; genetics ; metabolism ; pharmacology ; Cell Division ; drug effects ; Coculture Techniques ; DNA, Complementary ; genetics ; Humans ; Lymphoma, B-Cell ; metabolism ; pathology ; Recombinant Proteins ; pharmacology ; Time Factors ; Transfection ; Tumor Cells, Cultured ; drug effects

OBJECTIVE: To explore the genetic basis for a child featuring delayed intellectual development. METHODS: The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents. RESULTS: No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8. CONCLUSION The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; genetics ; DNA Copy Number Variations ; Developmental Disabilities ; genetics ; Facies ; Humans ; Hyperventilation ; genetics ; Intellectual Disability ; genetics ; Phenotype ; Transcription Factor 4 ; genetics

Objective To explore the genetic basis for a child featuring severe mental retardation.Methods The child was subjected to target region capture and next generation sequencing.Suspected variants were verified by Sanger sequencing.Results The child was found to harbor a hemizygous c.1A＞G (pMet1?) variation of the ARX gene,for which his mother was a heterozygous carrier.The mutation was unreported previously and was predicted to be "probably pathogenic" by bioinformatic analysis.Conclusion The c.1A＞G (pMet1?) variant of the ARX gene may underlie the occurrence of severe mental retardation in this child.

Objective:To analyze the clinical phenotype and genetic basis for a child featuring familial short stature.Methods:A child who was admitted to Huzhou Maternal and Child Health Care Hospital on October 7, 2021 for growth retardation and pectus carinatum was selected as the study subject. Physical exam and medical imaging was performed. The child was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 1-year-old male, had manifested with slightly short stature ( Z = -2.03), midfacial dysplasia, and multiple skeletal dysplasia such as pectus carinatum, irregular vertebral morphology, and defect of lumbar anterior bones. His mother, maternal grandmother and great-maternal grandfather also had short stature. WES revealed that the child has harbored a heterozygous c. 2858dupA (p.Asp953GlufsTer476) frameshifting variant of the ACAN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2858dup (p.Sp953Glufster476) variant was classified as likely pathogenic (PVS1+ PM2_Supporting). The patient has shown marked improved height after receiving 11 months of treatment with human recombinant growth hormone (supplemental dose) starting from 20 months of age. Conclusion:The ACAN: c. 2858dup (p.Asp953GlufsTer476) variant probably underlay the pathogenesis of short stature in this child.