Clinical and genetic analysis of a case with Thiamine metabolism dysfunction syndrome 5 / 中华医学遗传学杂志

OBJECTIVE@#To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5.@*METHODS@#Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay.@*RESULTS@#A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype.@*CONCLUSION@#A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.

Correlation between methylenetetrahydrofolate reductase gene polymorphism and Methotrexate toxicity in pediatric acute lymphoblastic leukemia in southern Fujian / 中华实用儿科临床杂志

Objective@#To explore the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX) chemotherapy in pediatric acute lymphoblastic leukemia (ALL).@*Methods@#From January 2015 to June 2018, 128 pediatric patients with ALL in southern Fujian who were admitted at the First Affiliated Hospital of Xiamen University were selected.Their peripheral blood 2 mL was collected and genomic DNA was extracted.The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method, and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria.@*Results@#Among 128 children, 54 cases(42.2%) presented rash, 48 cases (37.5%)with mucosal lesions, 51 cases (39.8%) with liver function damage, 23 cases (18.0%) with renal function damage, 52 cases (40.6%) with gastrointestinal reactions, 38 cases (29.7%)with leukopenia, 34 cases (26.6%) with thrombocytopenia and 63 cases (49.2%) with hemoglobin reduction.There was no significant difference in the incidence of MTX adverse reactions (rash, mucosa lesions, liver and renal function damage, gastrointestinal reaction, leukopenia, hemoglobin decrease and thrombocytopenia) between the MTHFR C677T and A1298C polymorphisms (all P>0.05). The different clinical risk (MTX dose) of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies (χ2=2.573, 2.264, 1.615, 0.267; all P>0.05). There was no significant difference among the abnormal incidence of MTX at 24 h, 48 h and 72 h (all P>0.05).@*Conclusions@#MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian, and its clinical application still needs further discussion.

Correlation betWeen methylenetetrahydrofolate reductase gene polymorphism and Methotrexate toxicity in pediatric acute lymphoblastic leukemia in southern Fujian / 中华实用儿科临床杂志

Objective To explore the association between methylenetetrahydrofolate reductase( MTHFR) C677T and A1298C gene polymorphisms and toxicity of Methotrexate(MTX)chemotherapy in pediatric acute lympho-blastic leukemia(ALL). Methods From January 2015 to June 2018,128 pediatric patients with ALL in southern Fu-jian who were admitted at the First Affiliated Hospital of Xiamen University were selected. Their peripheral blood 2 mL was collected and genomic DNA was extracted. The MTHFR genotype was detected by polymerase chain reaction(PCR) direct sequencing method,and the clinical significance of HD-MTX on ALL children with toxic and side effects was evaluated according to the National Cancer Institute-Common Toxicity Criteria. Results Among 128 children,54 cases (42. 2% )presented rash,48 cases(37. 5% )with mucosal lesions,51 cases(39. 8% )with liver function damage,23 ca-ses(18. 0% )with renal function damage,52 cases(40. 6% )with gastrointestinal reactions,38 cases(29. 7% )with leu-kopenia,34 cases(26. 6% )with thrombocytopenia and 63 cases(49. 2% )with hemoglobin reduction. There was no significant difference in the incidence of MTX adverse reactions(rash,mucosa lesions,liver and renal function damage, gastrointestinal reaction,leukopenia,hemoglobin decrease and thrombocytopenia ) between the MTHFR C677T and A1298C polymorphisms(all P>0. 05). The different clinical risk(MTX dose)of the children was not statistically signi-ficant in the MTHFR C677T and A1298C genotypes and allele frequencies( χ2 =2. 573,2. 264,1. 615,0. 267;all P>0. 05). There was no significant difference among the abnormal incidence of MTX at 24 h,48 h and 72 h(all P>0. 05). Conclusions MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL in southern Fujian,and its clinical application still needs further discussion.

Relationship between methylenetetrahydrofolate reductase gene polymorphism and methotrexate toxicities in childhood acute lymphoblastic leukemia chemotherapy / 临床儿科杂志

Objective To evaluate the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and susceptibility to methotrexate (MTX) adverse reaction in children with acute lymphoblastic leukemia (ALL) chemotherapy. Method The data bases of The Cochrane Library, PubMed, EMbase, EMCC, OVID, CNKI, VIP and WanFang Data were searched for relevant articles published in English and Chinese up to March 2016. Two researchers independently screened literature, extracted data, and assessed bias risk in the included studies. The RevMan 5.3 and Stata 12 software were used to analyze the association between gene polymorphism and the adverse reaction of MTX chemotherapy with the recessive, dominance, co-dominance, addition and allele gene model respectively. Results A total of 12 studies were included and all of them were case-control study, with 1419 cases in case group and 2188 cases in control group. The results of meta-analysis showed that the MTHFR gene polymorphism was unrelated to the untoward effect of neutropenia, thrombocytopenia, hemoglobin reduction, mucosal damage and liver function damage during MTX chemotherapy in children with ALL under the 5 analytical models. Under the co-dominance gene model, the association between MTHFR polymorphism C677T and overall adverse reaction of MTX was statistically significant (OR=1.39, 95％CI: 1.02～1.91, P=0.04). In the recessive gene model, the C677T polymorphism of MTHFR was associated with a reduced risk of gastrointestinal adverse reactions during MTX chemotherapy (OR=3.31, 95％CI: 1.03～10.59, P=0.04). In the dominance gene model, the C677T polymorphism of MTHFR was associated with a reduced risk of skin damage induced by MTX chemotherapy (OR=3.05, 95％CI: 1.25～7.41, P=0.01). Conclusion There is no significant association between the C677T polymorphism of MTHFR and the adverse effects of MTX chemotherapy, butfurther studies with larger sample size are needed.

Primary ciliary dyskinesia with HYDIN gene mutations in a child and literature review / 中华儿科杂志

Objective@#To review children′s primary ciliary dyskinesia (PCD) in the pathogenesis, clinical manifestation, diagnosis and treatment.@*Method@#To summarize and analyze the clinical data of a patient who was admitted to the first affiliated hospital of Xiamen University with primary ciliary dyskinesia in April 2014 while referring to related literature.@*Result@#An 11 years old boy, weighting about 22 kg, had a course of more than 10 years with repeated cough, stuffy and runny nose shortly after the birth. Examinations after admission to hospital showed that he presented with visible clubbing, bilateral paranasal sinus area tenderness, pharynx posterior wall with visible yellow pussy stuff drip and bilateral lung had scattered wet rales. Auxiliary examination revealed bilateral maxillary sinus, ethmoid sinus inflammation and bronchitis with left lower lung bronchiectasis. Fiberoptic bronchoscopy discovered congestion and a lot of sputum; ciliary biopsy pathology displayed that cilia were sparse and partial cilia 9+ 2 microtubules structural abnormalities. Full sequence of exon gene sequencing revealed two mutations located at chromosome 16 chr16: 71061369 (non-coding regions) and chr16: 70993591 (coding). Two novel mutations m. 3362A>G(E20) and c. 6101G>A(E39) in exon 16 of the HYDIN gene were identified. With the" ciliary motility disorder, gene" as keywords , the CNKI, Wanfang digital knowledge service platform and PubMed were searched for relevant articles from the establishment to July 2016. The studies retrieved included 9 cases and these cases were summarized. Comprehensive analysis showed that HYDIN gene mutations related PCD patients had the typical PCD performance such as repeatedly wet cough, sinusitis, bronchiectasis, and otitis media. The majority of patients have a history of acute respiratory distress syndrome in infancy and no visceral dislocation was not found. Most of the patients had no obvious structural abnormalities in cilia electron microscopic examination.@*Conclusion@#The PCD patients with HYDIN genes mutations have clinical manifestations such as sinusitis, otitis media, bronchiectasis but without transposition of viscera. Cilia structure can be normal under the electron microscopic examination in some of patients.

Advances in biosynthesis of 2-phenylethanol by yeasts / 生物工程学报

2-Phenylethanol (2-PE) is an aromatic alcohol with a pleasant rose-like fragrance. It has been widely used in food, cosmetic, and pharmaceutical industry. Most of 2-PE is produced by chemical synthesis, but the use of chemically synthesized product is restricted in some fields. 2-PE from plant extraction is natural but its production is very low. Microbial biotransformation is a promising process to produce natural 2-PE. In this paper, we review recent research progress in the synthetic metabolic pathways and regulatory processes of 2-PE in yeast, and strategies for improving 2-PE production. Moreover, we discuss the limitation of current progress and future research directions.

Congenital insensitivity to pain with anhidrosis in a family:2 cases report / 临床儿科杂志

Objective To report the clinical manifestation and gene mutation of congenital insensitivity to pain with anhidrosis (CIPA) in two patients from one family. Methods The data of clinical manifestation, laboratory examination, and family history of two patients were collected. The peripheral blood of patients and their parents were collected. Neurotrophic tyrosine kinase receptor type 1 (NTRK 1 ) gene was detected directly by Sanger method, the pathogenicity of the mutation in the gene was analyzed by bioinformatics. Results Both of patients were female and mainly suffered with reduplicated non-infectious fever, anhidrosis, insensitive to pain, and mental retardation. The proband had fracture many times after minor injury. The ninth exon of NTRK 1 genes in the proband and her younger sister were found to have heterozygous mutations, c. 851-33 T>A, as previously reported. Meanwhile, there was also found a new mutation, c. 1711 G>A (p.G 571 S), in thirteenth exon of NTRK 1 genes in these two patients. It was predicted to be a harmful mutation by bioinformatics and the mutation site is conservative. Their father and mother were found carrying the c. 851-33 T>A and c. 1711 G>A mutations respectively. Conclusion Both patients had typical clinical manifestations. And the newly discovered p.G 571 S mutation expands the mutation spectrum of NTRK 1 gene.