ABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations.@*METHODS@#A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3).@*CONCLUSION@#The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.
Subject(s)
Humans , Child , Male , Computational Biology , Diarrhea , Gene Frequency , Inflammatory Bowel Diseases/genetics , MutationABSTRACT
3-hydroxy-3-methylglutaric aciduria is a rare organic aciduria inherited by autosomal recessive trait.It is caused by the mutations in 3-hydroxy-3-methylglutaryl-CoA lyase gene.The clinical onset usually occurs in the neonatal and infant period.In recent years,with the development of technology for screening inherited metabolic diseases,the number of children with 3-hydroxy-3-methylglutaric aciduria are increasing.The incidence of this disease is about 1 ∶ 100 000 in reports of Europe and the United States.The incidence in China is unknown.In this paper,the advances on pathogenesis,clinical manifestations,diagnosis and treatment of 3-hydroxy-3-methylglutaric aciduria will be reviewed so as to improve the understanding of this disease and provide reference for its clinical diagnosis and treatment.
ABSTRACT
Biotinidase deficiency is an autosomal recessive genetic disease with the decrease of biotinidase activity,which is caused by mutations of biotinidase gene.In recent years,with the development of genetic metabolic disease screening,biotinidase deficiency has been diagnosed constantly.Its incidence is about 1 ∶ 60 000 persons overseas and its clinical manifestations are complicated with high mortality and morbidity.In this paper,advances on pathogenesis,clinical manifestations,diagnosis and treatment of biotinidase deficiency will be reviewed.