OBJECTIVE: To explore the clinical features and genetic basis for a child with early-onset Isolated sulfite oxidase deficiency (ISOD). METHODS: A child with ISOD who was admitted to Weihai Hospital Affiliated to Qingdao University on May 10, 2020 was selected as the study subject. Clinical data of the child was analyzed. The child and her parents were subjected to trio-whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: The female neonate was transferred to the intensive care unit due to "secondary pollution of amniotic fluid and laborious breathing for 11 minutes", and had developed frequent convulsions. Genetic testing revealed that she has harbored c.1200C>G and c.188G>A compound heterozygous variants of the SUOX gene, which were inherited from her mother and father, respectively. The c.1200C>G has been described previously and was rated as pathogenic based on guidelines from the American College of Medical Genetics and Genomics, whilst the c.188G>A variant was unreported previously and rated as variant of unknown significance. CONCLUSION The compound heterozygous variants of the SUOX gene probably underlay the ISOD in this child. Above finding has enriched the spectrum of SUOX gene variants and provided a basis for the clinical diagnosis and genetic counseling.
Female ; Humans ; Infant, Newborn ; Amino Acid Metabolism, Inborn Errors/diagnosis* ; Genetic Counseling ; Genetic Testing ; Mutation ; Oxidoreductases Acting on Sulfur Group Donors/genetics* ; Sulfite Oxidase/genetics*

Objective To analyze the safety of renal transplant from donors with primary central nervous system (CNS) tumors.Methods We retrospectively analyzed the clinical data of 33 donors with primary CNS tumors and the 63 corresponding renal recipients between January 2013 and December 2016 in Tongji Hospital.Results The mean period from diagnosis as primary CNS tumor to donation was about (21.8± 46.4) months (range:0.5 to 192.0 months).The pathological classification of these tumors included gliomas,meningioma,medulloblastoma,etc.Besides,there were 10 donors with high-grade CNS malignancies.Eleven donors have ever been through at least one of the four treatments (craniotomy,V-P/V-A shunt,radiotherapy and chemotherapy),14 donors have undergone none,and the clinical data of rest were unavailable.All the 63 recipients got well renal function after transplant.During an average follow-up of (15.9 ± 8.2) months (range:2.7 to 35.5 months),one recipient got donor-derived rhabdoid tumor 4 months posttransplant,underwent comprehensive treatments,including allograft nephrectomy,radiotherapy,chemotherpy and returned to hemodialysis,while the 62 cases got no donor-derived tumors.Conclusion Tumor transmission of renal allograft from donors with primary CNS tumors is inevitable but with low risk,which means this kind of donors can be used with careful assessment,full informed consent and good balance between wait-list death and tumor transmission.

A case of Usher syndrome with methylmalonic acidemia and homocysteine is reported. The patient was a two-month-old and small for gestational age male infant hospitalized for "feeding difficulties" during the neonatal period. The baby boy presented hypotonia, microcephaly, and hearing loss after birth. Genetic test found compound heterozygous mutations of c.482G>A and c.567dup in MMACHC, and both were pathogenic mutations inherited from his parents. Moreover, the patient also had compound heterozygous variants at c.2802T>G and c.14017T>C of USH2A gene. The former was suspected to be pathogenic, and the latter was of unknown clinical significance. Both were from the parents. Usher syndrome and methylmalonic acidemia with homocysteine were clinically diagnosed. Followed up to the age of two, the child was found with moderate mental retardation, while the physical development was comparable to that of the same age group.

Objective To investigate the feasibility and safety of the single kidney transplantation from pediatric donors to adult recipients.Methods From May 2013 to January 2017,a total of 50 single kidney transplants from pediatric donation after citizen death (DCD) donors of age between 3 to 12 years to adult recipients were performed and the data were summarized.Results The average age of donors was 6.4 ± 2.5 years with an average donor weight of 19.1 ± 5.9 kg,and the average kidney length was 6.3 ± 0.6 cm.For the 50 adult recipients,the average age was 38.5 ± 12.1 years,the average body weight was 56.1 ± 13.1 kg,and the number of female patients was 26 (52％).All except 3 of these patients were transplanted for the first time.Delayed graft function (DGF) was observed in 15 patients (30％).The average value of eGFR among all the patients was rapidly increased in the first 3 months after transplantation and then steadily increased to (82.3 ± 13.4) mL· min-1·1.73 m-2 at 1 st year,followed by (83.8 ± 22.5) mL· min-1·1.73 m-2 at 2nd year.Four renal grafts developed acute rejection (8％),and 3 of them were successfully reversed by the treatment.Pulmonary infection occurred in 4 recipients,and 2 died.During a follow-up period of 19 months,uncensored grafts survival was 94％,and patients survival was 96％.Conclusion Excellent intermediate-term transplant outcome can be achieved by using single kidneys from pediatric donors elder than 3 years,which may shorten the waiting time in adult recipients and alleviate the contradictions in the absence of suitable pediatric recipients.

Objective To evaluate the efficacy of tigecycline plus prolonged high-dose meropenem infusion in the prevention and treatment of early carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after renal transplantation .Methods From January 2016 to December 2018 ,clinical data were retrospectively analyzed for 13 renal transplant recipients with graft-carried CRKP .The relevant clinical data included treatments and outcomes of grafts and recipients .KPC-2 gene was the only resistance gene detectable in all isolates of CRKP . Among 13 CRKP positive recipients ,there were positive cultures of graft preservation solution ,recipient blood & urine (n=1) , positive cultures of graft preservation solution & urine (n=1) ,positive cultures of graft preservation solutions & peri-graft drainage (n=3) ,continuous positive cultures of peri-graft drainage more than twice (n= 3) and positive culture of graft preservation solution (n= 5).All patients received tigecycline plus prolonged high-dose meropenem infusion-based antibiotics .Results Five patients with CRKP positive in preservation solution were successfully prevented from infection after a treatment period of (12 .4 ± 2 .1)days .Among another 8 cases ,additional topical medications (n= 3) and surgical debridement (n= 1) were used .It took a median time of 16 (7～60) days until a negative culture and the total antibiotic treatment course was 20 (10～93) days .The average hospitalization duration was (50 ± 35) days .During a median follow-up period of 25 (6～28) months ,there was no onset of renal arterial rupture ,graft nephrectomy or death .The survival rate was 100％ for recipients and 92 .3％ for grafts .Conclusions For post-transplant infections due to graft-carried KPC-2 producing CRKP ,rapid diagnostics and tigecycline plus prolonged high-dose meropenem infusion may optimize clinical outcomes by decreasing the rate of graft nephrectomy and the recipient mortality .

Objective To investigate the value of different biopsy methods for quality evaluation of the donated kidney organ after citizen death.Methods Six cases (6 pairs) of discard donor kidneys were collected from October 2016 to May 2017,respectively,and grouped by wedge biopsy and core needle biopsy.After being fixed and processed for routine paraffin embedding and hematoxylin-eosin (H&E) staining,the specimens were evaluated by the qualified rate of sample,the number of glomerulus,sclerotic glomerulus and small arteries.Results The comparison of two different biopsy methods showed that the number of samples obtained by wedge biopsy was 30.There were 29 samples which were qualified and the qualification rate was 96.7％.The number of samples obtained by core needle biopsy was 30,and only 21 samples were qualified and the qualification rate was 70％.In the wedge biopsy samples,the average number of glomeruli was 22.1 and 6.9 of them were sclerotic glomeruli.The ratio of sclerotic glomeruli was 31.3％.The average number of glomeruli in core needle biopsy samples was 9.5 and 2.1 of them were sclerotic glomeruli.The ratio of sclerotic glomeruli was 22.1 ％.The average number of arteries in wedge biopsy samples was 5.4,and that in core needle biopsy samples was 3.9.The results indicated that the qualification rate of wedge biopsy was significantly higher than that of core needle biopsy (P＜0.01).The number of glomeruli,sclerotic glomeruli and small arteries in wedge biopsy samples was significantly greater than than in core needle biopsy (P＜0.05).Conclusion Wedge biopsy was superior to core needle biopsy for the quality evaluation of specimens and identifying clinically significantly histopathological findings.Thus it is potential for wedge biopsy to become the main method in pre-implantation histopathological evaluation.

OBJECTIVE: To explore the characteristics of mutations of four common pathogenic genes (GJB2, SLC26A4, GJB3 and 12S rRNA) among patients with nonsyndromic hearing loss (NSHL) from eastern Shandong. METHODS: Peripheral blood samples of 420 NSHL patients were collected, and a hereditary-deafness-gene microarray was used to detect GJB2 c.235delC, c.299-300delAT, c.35delG and c.176del16 mutations, GJB3 c.538C>T mutation, SLC26A4 c.2168A>G and c.IVS7-2A>G mutations, and 12S rRNA c.1555A>C and c.1494C>T mutations. For patients carrying single heterozygous mutations, the coding regions of the above genes were analyzed with Sanger sequencing. RESULTS: The results of the microarray assay and Sanger sequencing showed that 84 patients (20.00%) carried GJB2 mutations, with c.235delC (16.43%) and c.299-300delAT (7.86%) being most common. Seventy-five patients (17.86%) carried SLC26A4 mutations, for which c.IVS7-2A>G accounted for 15.71%. In addition, 5.95% of patients carried 12S rRNA mutations. Only one patient was found to carried GJB3 mutation (c.538C>T). CONCLUSION Common pathogenic mutations for NSHL in eastern Shandong included GJB2 c.235delC and SLC26A4 c.IVS7-2A>G. Of note, 5.95% of patients were due to 12S rRNA m.1555A>G mutation, which gave a frequency greater than other regions of China.
China ; Connexin 26 ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Deafness ; Genes, rRNA ; Hearing Loss ; Humans ; Mutation ; RNA, Ribosomal ; Sulfate Transporters

Objective: To analyze the characteristics of the second primary tumor affecting the survival of patients with lymphoma, and to explore the risk factors of death from the second primary tumor. Methods: The medical records and related death information of 1 173 lymphoma patients who had already died with known causes were collected. The basic causes of death and the characteristics of patients who died of the second primary tumor were analyzed. Cox regression model was used to analyze the risk factors of lymphoma patients who died of the second primary tumor. Results: Among the 1 173 patients who had died, 94 (8.0%) died of the second primary tumor, 935 (79.7%) died of the primary lymphoma and 144 (12.3%) died of other diseases. The second primary tumor accounted for 17.5% (38/217) of all causes of death in patients with the survival period of more than 5 years, and the second primary tumor accounted for 28.3% (17/60) of all causes of death in patients with the survival period of more than 10 years. Among 94 cases who died of second primary tumors, 31 died of lung cancer, 15 died of gastric cancer, 13 died of liver cancer, 9 died of pancreatic cancer, 6 died of colorectal cancer, 6 died of second primary lymphoma and 14 died of other types of tumors. Univariate Cox regression analysis showed that age, first-line treatment effect, and chest or mediastinal radiotherapy were associated with the death from second primary tumors for lymphoma patients (all P<0.05). Multivariate Cox regression analysis showed that the effect of first-line treatment (P=0.030) and the chest or mediastinal radiotherapy (P=0.039) were independent factors for the death of lymphoma patients from the second primary tumor. Conclusions The second primary tumor is an important factor affecting the survival of lymphoma patients, and the risk of death from second primary tumors increases significantly over time. The effect of first-line treatment and radiotherapy in the chest or mediastinum are independent factors for the death of lymphoma patients from the second primary tumor.