OBJECTIVE: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.
Cell Cycle Proteins ; genetics ; De Lange Syndrome ; genetics ; Genetic Testing ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Mutation ; Phenotype

Objective To discuss the clinical characteristics,pathogenesis,diagnosis and treatment of preterm ovarian hyperstimulation syndrome (POHS).Method The process of diagnosis and treatment of a test-tube female baby were summarized.She was deliveried at 32+2 weeks of gestation,diagnosed with POHS,and born in the First Affiliated Hospital of Wenzhou Medical University(in 2015).Retrieval of related literature in PubMed database and Wanfang database was performed using the key words "ovarian hyperstimulation syndrome" and " preterm infants or newborns" from 1980 to 2015.Result The patient developed labial hyperemia and edema,ectropion of vaginal mucosa and plica,swelling of the hypogastrium and upper legs at 41 days (38+1 weeks post-conception).The child was continuously observed because diagnosis was not clear.The pelvic and abdominal ultrasonography examinations revealed a cyst in the right ovary and laboratory evaluation of the baby showed high concentrations of gonadotropin and estradiol at 49 days (39+2 weeks post-conception),and thus the baby was diagnosed with POHS.With no special intervention measures,the baby became normal at 169 days (4 months post-conception).Six papers from foreign literature were retrieved and none from Chinese literature,which reported 12 cases of POHS.They all characterized prematurity,ovarian cyst/cysts,labial hyperemia and edema,swelling of the hypogastrium and upper leg,high serum gonadotropin and estradiol levels at 35 to 39 weeks post-conception,including 3 cases with breast enlargement,1 case with vaginal bleeding and 1 case with ectropion of vaginal mucosa and plica.The treatments included in 1 case combined surgery with pharmacological intervention,in another case only pharmacological intervention,and in the others no interventional measures were taken but were only followed up.As for the results,the baby with the surgical treatment had recurrence,but the symptoms,ovarian cyst and hormone concentration of the other babies gradually became normal in 4-5 months.Conclusion POHS is a rare and self-limiting disease.The common clinical features of this disease are prematurity,ovarian cyst or cysts,labia hyperemia and edema,swelling in the hypogastrium and upper legs,high serum gonadotropin and estradiol levels at 35 to 39 weeks post-conception.It does not require treatment if there is no complication,but follow-up is necessary.