HBV reactivation is commonly seen during immunosuppressive therapy and is associated with high incidence and mortality rates due to hepatitis outbreak and liver decompensation, and therefore, it should be taken seriously. However, the prevention and management of this potential complication is still a difficulty in clinical practice. This article reviews the diagnostic criteria and clinical outcomes of HBV reactivation, discusses the association of immunosuppressive therapy with the risk of HBV reactivation, and outlines the strategies for the prevention of HBV reactivation and recent advances. It is pointed out that early identification of patients with HBV infection before immunosuppressive therapy is of vital importance, and the initiation of antiviral therapy at the right moment based on risk stratification can effectively reduce the risk of HBV reactivation. We hope that this review can increase the awareness of HBV reactivation among clinicians and provide an effective reference for optimizing the management and prevention of HBV infection.

Objective To explore the genetic basis for a neonate featuring global developmental delay.Methods Clinical and laboratory tests were carried out for the patient.Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA.Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases.Suspected variant was validated by Sanger sequencing.Results The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance.Genetic testing revealed two novel variants of the SLC19A3 gene in him,namely c.448G＞ A and c.169C＞T.The amino acids encoded by the two codons are highly conservative,and both variants were predicted to be pathogenic by bioinformatic analysis.Conclusion The compound heterozygous c.448G＞A and c.169C＞T variants probably underlay the onset of disease in the patient.Above finding also enriched the variant spectrum of SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.

OBJECTIVETo explore the genetic cause of a Chinese boy with unexplained mental retardation, and analyze the pattern of inheritance for his family.

METHODSRoutine karyotyping, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) were used to detect chromosome abnormalities in the patient and his families.

RESULTSChromosome analysis suggested that the proband and 7 affected individuals had an identical karyotype 46,XN,der(22)t(3;22)(q28;q13)pat, while his father and 5 other relatives carried a same karyotype of 46,XN,t(3;22)(q28;q13). His mother and other family members were normal. CMA analysis confirmed that the patient had a 9.0 Mb duplication at 3q28q29, in addition with a 1.7 Mb deletion at 22q13.3. Above results were confirmed by FISH.

CONCLUSIONThe abnormal phenotypes of the proband and his family members from five generations have conformed to those of 3q duplication and 22q13.3 deletion caused by unbalanced translocation involving chromosomes 3q and 22q. The presence of multiple patients in this family may be attributed to abnormal gametes produced by parental balanced translocations involving 3q and 22q.

Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Family Health ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Pedigree ; Translocation, Genetic

OBJECTIVETo investigate the genetic cause for a child with developmental delay and congenital heart disease through molecular cytogenetic analysis.

METHODSG-banded karyotyping and chromosomal microarray analysis (CMA) were performed for the patient and his parents.

RESULTSThe proband's karyotype was detected as ring chromosome 3, and a 3q26.3-25.3 deletion encompassing 45 genes has been found with CMA. Testing of both parents was normal.

CONCLUSIONClinical phenotype of the patient with ring chromosome 3 mainly depends on the involved genes. It is necessary to combine CMA and karyotyping for the diagnosis of ring chromosome, as CMA can provide more accurate information for variations of the genome.

Chromosomes, Human, Pair 3 ; genetics ; Cytogenetic Analysis ; methods ; Cytogenetics ; methods ; Developmental Disabilities ; genetics ; Female ; Heart Defects, Congenital ; genetics ; Humans ; Infant ; Karyotyping ; methods ; Ring Chromosomes ; Syndrome

OBJECTIVETo explore the genetic cause for a boy featuring mainly with mental retardation.

METHODSG-banding karyotyping and fluorescence in situ hybridization (FISH) were carried out for the child and his parents. The child was also analyzed with chromosome microarray (CMA). Suspected microdeletion was validated with quantitative PCR.

RESULTSThe proband was found to have a 47,XYY karyotype by both chromosome and FISH analyses, while both of his parents had a normal karyotype. CMA suggested that the proband had one copy of X chromosome and two copies of Y chromosome. In addition, CMA has also detected deletion of the KYNU gene (mapped at 2q22.2), which could be pathogenic. The result was confirmed by qPCR.

CONCLUSIONFor its high resolution, CMA can be used to identify potential microdeletion/duplications among children with chromosome aneuploidy and unusual phenotypes.

Adult ; Child, Preschool ; Chromosome Banding ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Sex Chromosome Disorders ; diagnosis ; genetics ; XYY Karyotype ; diagnosis ; genetics

OBJECTIVE: To explore the genetic basis of a patient presenting with dysmorphism, intellectual disability, psychomotor delay and hypoplasia of corpus callosum by using next generation sequencing. METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his family members and subjected to exome sequencing. Suspected variants were verified with Sanger sequencing. RESULTS: The patient was found to carry a heterozygous c.1357delAinsGGA variant in exon 11 of the TCF4 gene, which was verified as de novo by Sanger sequencing. The variant may result in a truncated protein and affect its function. CONCLUSION The heterozygous c.1357delAinsGGA variant the TCF4 gene probably underlies the disease in the proband.
Facies ; Genetic Testing ; Humans ; Hyperventilation/genetics* ; Intellectual Disability/genetics* ; Male ; Transcription Factor 4/genetics*

OBJECTIVE: To explore the genetic basis for a neonate featuring developmental delay. METHODS: Clinical examination and laboratory tests were carried out for the patient. Peripheral venous blood samples of the proband and his parents were extracted and subjected to target capture next generation sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a four-month-old male, has presented with developmental delay and weakness of limbs. Genetic testing revealed that he had harbored a novel c.1432C>T variant of the TNPO3 gene, which was inherited from his mother. The nonsense variant has resulted in premature termination of protein translation and was predicted to be pathogenic by bioinformatics analysis. CONCLUSION The heterozygous c.1432C>T variant of the TNPO3 gene probably underlay the limb-girdle muscular dystrophies form 1F in this patient. Above finding has enriched the variation spectrum of the TNPO3 gene.
Genetic Testing ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Muscular Dystrophies, Limb-Girdle/genetics* ; Mutation ; Phenotype ; beta Karyopherins/genetics*

OBJECTIVE: To explore the clinical features and molecular basis of a Chinese pedigree with two siblings affected by cytochrome P450 oxidoreductase deficiency (PORD). METHODS: Clinical features of the patients were reviewed, and their genomic DNA was subjected to next generation sequencing (NGS). RESULTS: The two siblings presented peculiar facies, genital hypoplasia and skeletal deformity. NGS revealed that both have carried compound heterozygous variants of the POR gene, namely c.1370G>A and c.517-19_517-10delGGCCCCTGTGinsC, which were respectively inherited from their parents. CONCLUSION Both siblings were diagnosed with PORD based on sequencing of the POR gene. The newly discovered POR c.517-19_517-10delGGCCCCTGTGinsC has enriched the spectrum of PORD-related genetic variants.

OBJECTIVE: To explore the genetic basis for a child featuring short stature. METHODS: G-banded karyotyping, chromosomal microarray analysis (CMA) and high-throughput sequencing were carried out on peripheral blood sample from the child. RESULTS: The karyotype of the child was ascertained as 45,XY,-4[3]/46,XY,r(4)(p16q35)[84]/47,XY,-4,r(4)(p16q25)*2[7]/48,XY,-4,r(4)(p16q35)*3[1]/46,XY,dic r(4;4)(p16q35;p16q35)[2]/46,XY,add(4)(p16)[3]. A 647 kb deletion at 4p16.3 was identified by CMA, which encompassed 6 OMIM genes including ZNF141, PIGG, PDE6B, ATP5I, PCGF3 and MYL5. High-throughput sequencing has identified no pathogenic/likely pathogenic variants consistent with the clinical symptoms. CONCLUSION A rare ring chromosome 4 syndrome was identified by combined chromosomal karyotyping, CMA and high-throughput sequencing. Conventional cytogenetic analysis and genetic testing in combine have enabled the diagnosis in this case.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese girl featuring mental retardation, intellectual disability, language development delay and epilepsy. METHODS: G-banded chromosomal karyotyping was carried out for the child. Genomic DNA of the patient and her parents was extracted and subjected to high-throughput sequencing. The results were analyzed with bioinformatic tools and validated by Sanger sequencing. RESULTS: The karyotype of the child was ascertained as 46,XX. Sequencing result showed that she has carried a de novo heterozygous c.1861C>T (p.R621X) variant of the SYNGAP1 gene. CONCLUSION The nonsense variant c.1861C>T (p.R621X) of the SYNGAP1 gene probably underlies the disease in this child. Above result has enabled genetic diagnosis and counseling for her family.