De novo mutation loci and clinical analysis in a child with sodium taurocholate cotransport polypeptide deficiency: A case report

BACKGROUND Sodium taurocholate cotransport polypeptide(NTCP)deficiency disease is a genetic metabolic disorder due to mutations in the SLC10A1 gene and impaired bile acid salt uptake by the basolateral membrane transport protein NTCP in hepatocytes.A variety of clinical manifestations and genetic mutation loci have been reported for this disease.However,specific therapeutic measures are lacking,and the long-term effects are unknown.CASE SUMMARY An infant with elevated bile acids and behavioral neurodevelopmental delay failed to respond to bile acid-lowering therapy.Genetic testing for metabolic liver disease revealed that the child had NTCP deficiency due to the SLC10A1 mutation:c.422dupA(p.Y141X),which is a novel mutation site.The current followup revealed a gradual decrease in bile acid levels after 1 year of age,but the child still had behavioral neurodevelopmental delays.CONCLUSION The clinical manifestations,genetic characteristics,treatment and long-term prognosis due to NTCP deficiency remain poorly defined and need to be further confirmed by more studies and reports.

Methyl-CpG-Binding protein 2 duplication syndrome in a Chinese patient:A case report and review of the literature

BACKGROUND Chromosomal Xq28 region duplication encompassing methyl-CpG-binding protein 2(MECP2)results in an identifiable phenotype and global developmental delay known as MECP2 duplication syndrome(MDS).This syndrome has a wide range of clinical manifestations,including abnormalities in appearance,neurodevelopment,and gastrointestinal motility;recurrent infections;and spasticity.Here,we report a case of confirmed MDS at our institution.CASE SUMMARY A 12-year-old Chinese boy presented with intellectual disability(poor intellectual[reasoning,judgment,abstract thinking,and learning]and adaptive[lack of communication and absent social skills,apraxia,and ataxia]functioning)and dysmorphism.He had no history of recurrent infections,seizures,or bowel dysfunction,which is different from that in reported cases.Microarray comparative genomic hybridization confirmed MECP2 duplication in the patient and his mother who is a carrier.The duplication size was the same in the patient and his mother.No prophylactic antibiotic or anti-seizure therapy was offered to the patient or his mother before or after the consultation.CONCLUSION MDS is rare and has various clinical presentations.Clinical suspicion is critical in patients presenting with developmental delays.

Prenatal PM_(2.5)Exposure Associated with Neonatal Gut Bacterial Colonization and Early Children’s Cognitive Development

Previous research indicated that fine particulate matter(PM_(2.5))exposure affected both offspring neurodevelopment and the colonization of gut microbiota(GM),while the underlying mechanism remained unclear.Our study aimed to evaluate the impacts of prenatal PM_(2.5) exposure on child cognitive development and investigate the role of neonatal GM colonization in the association.Based on the Shanghai Maternal−Child Pairs Cohort,361 maternal−child pairs were recruited.Prenatal PM_(2.5) exposure concentrations were estimated using a high-spatial-resolution prediction model,and child neurodevelopment was assessed by the Ages and Stages Questionnaire.Multivariable linear regression models,logistic regression models,linear discriminant analysis effect size,and random forest model were applied to explore the associations among PM_(2.5) exposure,GM colonization,and children’s neuro-development.The present study revealed a negative correlation between PM_(2.5) exposure throughout pregnancy and child neurodevelopment.Prenatal PM_(2.5) exposure was associated with an increased risk of suspected developmental delay(SDD)(OR=1.683,95%CI:1.138,2.489)in infants aged 2 months.Additionally,potential operational taxonomic unit markers were identified for PM_(2.5)-related neurotoxicity,demonstrating promising classification potential for early SDD screening(AUC=71.27%).Prenatal PM_(2.5) exposure might disrupt the composition,richness,and evenness of meconium GM,thereby influencing cognitive development and the occurrence of SDD in offspring.Seven PM_(2.5)-related genera,Ruminococcus gnavus group,Romboutsia,Burkholderiaceae Caballeronia Paraburkholderia,Blautia,Alistipes,Parabacteroides,and Bacteroides,were validated as correlated with prenatal PM_(2.5) exposure and the occurrence of SDD.Moreover,alterations of GM related to PM_(2.5) exposure and SDD might be accompanied by changes in functional pathways of amino acid,lipid,and vitamin metabolism as indicated by differentially enriched species in the Kyoto Encyclopedia of Genes and Genomes.