Objective:To investigate the prognosis and outcome of patients with chronic hepatitis C (CHC) related cirrhosis after achieved sustained virologic response (SVR) treated with direct-acting antiviral agent (DAA).Methods:Ninety-five patients diagnosed with CHC related cirrhosis who had complete data in Tianjin Second People′s Hospital from January 2014 to June 2017 were retrospectively followed up. Among them, 72 patients were treated with DAA and all of them achieved SVR, and the other 23 patients did not receive any antiviral therapy. The differences of mortality and incidence of hepatocellular carcinoma (HCC) between DAA treatment group and non-antiviral treatment group were compared. Statistical analysis was performed by independent sample t test, Mann-Whitney U test and chi-square test. Results:At the end of follow-up for three to 71 months, patients in DAA treatment group had a significant improvements in alanine aminotransferase, aspartate aminotransferase, albumin and liver stiffness measurement compared with those before treatment (42(23, 61) U/L vs 18(13, 28) U/L, 54(37, 75) U/L vs 23(18, 28) U/L, 39(33, 42) g/L vs 45(41, 48) g/L, 26(18, 37) kPa vs 15(11, 26) kPa, respectively, Z=-6.005, -7.008, -6.057 and -3.162, respectively, all P<0.01). However, there were no significant differences in incidence of HCC (12%(9/72) vs 17%(4/23)) and mortality (3%(2/72) vs 13%(3/23)) between the DAA treatment group and non-antiviral treatment group (both P>0.05). There was no significant difference of cumulative incidence of HCC in DAA treatment group compared with non-antiviral treatment group ( P=0.609). The age of patients progressed to HCC was older than those without HCC ((60.3±3.6) years vs (54.4±9.9) years, t=-3.948, P<0.01). In subgroup analysis, among the six patients with HCC, four had diabetes, the prevalence of diabetes in the patients without HCC was 17%(7/42); the level of fasting blood glucose (FBG) ((7.3±1.9) mmol/L vs (5.9±1.1) mmol/L) were higher in patients progressed to HCC than those without HCC in DAA treatment group with compensated cirrhosis ( χ2=7.430 and t=-2.442, respectively, both P=0.019). Conclusions:DAA treatment could notably improve liver function and alleviate liver fibrosis, but could not reduce the mortality and incidence of HCC in patients with CHC related cirrhosis significantly. Diabetes and high level FBG may be the risk factors for occurrence of HCC in patients with CHC related compensated cirrhosis.

OBJECTIVE: To carry out variant analysis for a Chinese boy featuring dyshormonogenesis due to congenital hypothyroidism. METHODS: DNA of the patient and his parents was extracted and sequenced by high-throughput sequencing. The results were validated with Sanger sequencing and analyzed with Bioinformatics software. RESULTS: Sequencing result showed that the patient has carried compound variants of c.2654G>T(p.Arg885Leu) and c.943G>T(p.Gly315X) of the DUOX2 gene, which were inherited respectively from his mother and father. CONCLUSION The missense mutation c.2654G>T and nonsense mutation c.943G>T probably underlie the disease in this child.
Child ; Congenital Hypothyroidism ; diagnosis ; genetics ; Dual Oxidases ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mutation, Missense

Clinical treatment of large segmental bone defect has always been a major challenge for the medical community,which is due to the complex and diverse pathogenic factors of large segmental bone defect.In recent years,the clinical treatment of large segmental bone defect has made great progress,and the main treatment options include vascularized or non-vascularized autologous bone grafts,allograft bone transplantation,masquelet technology,llizarov technology and bone tissue engineering.Therefore,understanding the advantages and disadvantages of various treatment options is very important for the clinical treatment of large bone defects in long bones,laying the foundation for clinical treatment.

Objective To discuss clinical characteristics of a family with Xia-Gibbs syndrome, test and analyze the mutation of their pathogenic gene, and to explore the clinical and genetic characteristics of Xia-Gibbs syndrome. Methods A patient with unexplained developmental retardation was clinically examined and the medical history of his family was collected. Genetic detection was performed to analyze his genetic causes. Results The proband, who was two-year and 1-month old, displayed unusual facies, hypotonia and unexplained developmental retardation. Brain MRI showed leukodystrophy. Other members of his family had no similar medical history. And the proband was found to carry the de novo mutation of c.1073dupC in AHDC1 gene. Conclusion This is the first case with Xia-Gibbs syndrome caused by AHDC1 mutation in China, which has a great significance in studying the correlation between genotype and phenotype.

OBJECTIVETo explore the clinical and genetic features of a Chinese boy featuring X-linked mental retardation.

METHODSClinical features of the patient were analyzed. The DNA of the patient and his parents was extracted and sequenced by next generation sequencing. The results were validated and analyzed with software.

RESULTSThe child displayed X-linked mental retardation. Sequencing showed the patient has carried a c.455T>C (p.L152P) mutation of the GRIA3 gene inherited from his mother.

CONCLUSIONThe c.455T>C (p.L152P) mutation of the GRIA3 gene probably underlies the X-linked mental retardation in this child.

Child, Preschool ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Male ; Mental Retardation, X-Linked ; genetics ; Mutation ; Receptors, AMPA ; genetics

OBJECTIVETo explore the genetic cause and clinical features of a neonate with bullous congenital ichthyosiform erythroderma.

METHODSThe patient was examined thoroughly. Following the extraction of genomic DNA, next generation sequencing was performed to analyze the genetic cause.

RESULTSThe patient manifested generalized erythema, blistering, and extensive exfoliation of the skin. A heterozygous missence 482T>G mutation was found in the first exon of KRT10 gene, which led to a p.L161W alteration in its protein product.

CONCLUSIONThe de novo mutation of the KRT10 gene probably underlies the disease in the child.

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay. METHODS: DNA was extracted from peripheral blood sample taken from the patient and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: A heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene was detected in the proband, which was a verified to be de novo in origin. CONCLUSION The heterozygous c.239T>C (p.Ile80Thr) variant of the GNB1 gene probably underlay the disease in this child.
Arthrogryposis ; Child ; Family ; GTP-Binding Protein beta Subunits ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Whole Exome Sequencing

OBJECTIVETo explore the clinical and genetic features of a Chinese boy with oculocutaneous albinism.

METHODSThe clinical features of the patient were analyzed. The DNA of the patient and his parents was extracted and sequenced by next generation exome capture sequencing. The nature and impact of detected mutation were predicted and validated.

RESULTSThe child has displayed strabismus, poor vision, nystagmus and brown hair. DNA sequencing showed that the patient has carried compound heterozygous mutations of the TYRP1 gene, namely c.1214C>A (p.T405N) and c.1333dupG, which were inherited from his mother and father, respectively. Neither mutation was reported previously.

CONCLUSIONThe child has suffered from oculocutaneous albinism type Ⅲ caused by mutations of the TYRP1 gene.

Albinism, Oculocutaneous ; diagnosis ; genetics ; Amino Acid Sequence ; Base Sequence ; Child, Preschool ; Exome ; genetics ; Family Health ; Female ; Heterozygote ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Mutation ; Oxidoreductases ; genetics ; Parents

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 explore the genetic basis for a child with clinically suspected nephronophthisis (NPHP). METHODS: Peripheral blood samples of the patient and her parents were collected subjected to high-throughput sequencing. Sanger sequencing was used to verify the gene variants. RESULTS: The patient, a 7-year-old girl with congenital blindness, was admitted to a local hospital due to repeated vomiting for 7-8 days and then transferred to author's hospital due to renal failure. Her urine occult bloods (3+) and urine protein (1+) were abnormal. Her blood urea nitrogen and creatinine showed a significant progressive increase. Renal ultrasound showed a mild enlargement in bilateral renal, increased echogenicity, loss of corticomedullary differentiation, and the presence of cysts in both kidneys. No familial genetic history was found in the family of patient and the child was clinically diagnosed with nephronophthisis. The proband was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2587-2A>T and c.2251C>T, which were inherited from her mother and father, respectively. Based on the ACMG guidelines, both variants were predicted to be pathogenic. CONCLUSION The patient was diagnosed with NPHP type 6 due to variants of the CEP290 gene. Above finding has provided new evidence for the genotype-phenotype correlation of this disease.