Microcephaly-seizures-development delay syndrome in a pedigree: genetic analysis and literature review / 中华围产医学杂志

Objective:To analyze the phenotypes and genetic etiology of microcephaly- seizures-development delay (MCSZ) syndrome.Methods:The patient was diagnosed with MCSZ syndrome in June 2018 at Shenzhen Maternity and Child Healthcare Hospital. She was the couple's first child, and the mother conceived a second child in 2020. The clinical data of the proband were retrospectively analyzed, and the bioinformatics analysis and whole-exome sequencing (WES) were performed on the proband and her parents to identify the pathogenic variants, which were further validated using Sanger sequencing. The prenatal genetic diagnosis of the second fetus was performed following the molecular diagnosis of the proband was confirmed. The clinical manifestations and pathogenesis of MCSZ syndrome were summarized by reviewing related literature.Results:(1) Case report: The patient, an eight-month-old girl, was admitted to our hospital due to microcephaly and repeated seizures. Another clinical characteristic was mental retardation. Auditory evoked potential detected moderate impairment of the left auditory nerve pathway. WES showed a compound heterozygous variation in the PNKP gene of the proband. Moreover, the pathogenic variation, c.199-10_203delinsTCTGAGGGGT, was inherited from the father, and the likely pathogenic variation, c.1505C>T(p.P502>L), was inherited from the mother, which was both de novo mutations. The compound heterozygous variation in the PNKP gene was considered genetic etiology based on the genetic testing and clinical features. Prenatal diagnosis showed that the second fetus did not inherit the PNKP gene variants from the parents and the couples chose to continue the pregnancy. A girl was born, and her psychomotor development and occipitofrontal size circumference were normal at 13 months old. (2) Literature review: 39 MCSZ syndrome cases were retrieved, including the present case and 38 cases from 12 relevant literature. The clinical characteristics were microcephaly (91.7%, 33/36), seizures (88.2%, 30/34), development delay (96.4%, 27/28), hyperactivity (25.6%, 9/39), gastroesophageal reflux (10.3%, 4/39), and hearing loss (7.7%, 3/39). Most patients' first onset of epilepsy was in infancy (96.3%, 26/27). Cranial MRI examination showed brain dysplasia in 31 cases (91.2%, 31/34). Conclusions:When the fetal head circumference is smaller than normal and is progressively reduced combined with postnatal microcephaly, epilepsy, developmental retardation, hyperactivity disorder, gastroesophageal reflux, and hearing loss, MCSZ syndrome should be considered. The prognosis varies widely, and genetic testing facilitates the early diagnosis and genetic counseling of MCSZ syndrome.

Correlation between rs17118 polymorphism of XYLB gene and ischemic stroke in a Chinese Han population / 国际脑血管病杂志

Objective To verify the correlation between rs17118 polymorphism of xyluloknase homolog (XYLB) gene and risk of ischemic stroke in a Chinese Han population.Methods A case-control study design was used.The case group was the patients with first-ever ischemic stroke and the control group was the healthy subjects from hospital physical examination.Taqman probe fluorescence quantitative polymerase chain reaction technique was used to detect the genotype distribution of rs17118 C/A polymorphisms.Results A total of 475 patients with ischemic stroke and 483 controls were enrolled in the study.The proportion of hypertension (67.9％ vs.22.2％;x2 =292.982,P ＜ 0.001) and diabetes (24.2％ vs.7.3％;x2 =25.864,P ＜ 0.001),as well as the levels of triacylglycerol (1.649 ± 1.126 mmol/L vs.1.157 ±1.480 mmol/L;t=3.592,P＜0.001),and low-density lipoprotein cholesterol (3.499 ± 1.163 mmol/L vs.3.105 ± 0.627 mmol/L;t =-6.227,P ＜ 0.001) in the case group were significantly higher than those in the control group,but the total cholesterol level was significantly lower than that in the control group (5.144 ± 1.296 mmol/L vs.5.491 ± 1.335 mmol/L;t =4.650,P ＜ 0.001).The AA genotyp e (11.4％ vs.7.5 ％;x2 =6.136,P =0.016) and A allele (32.3 ％ vs.26.4％;x2 =8.093,P =0.005) frequencies in the case group were significantly higher than those in the control group.Multivariatelogistic regression analysis showed that after adjusting for traditional risk factors,the risk of ischemic stroke in AA genotype carriers was 1.97 times of the CC genotype carriers (odds ratio 1.971,95％ confidence interval 1.040-3.736,P=0.038).Conclusions The rsl7118C/A polymorphism of XYLB gene may be associated with the risk of ischemic stroke in the Chinese Han population.

Expression autophagy-related gene pULK and PI3KC3 and their correlation with human non-small-cell carcinoma / 天津医药

Objective To examine expression levels of autophagy gene pULK and PI3KC3 and to explore their correla?tion with non-small cell lung cancer (NSCLC). Methods A total of 77 samples of surgical resection from NSCLC speci? mens (including 31 cases of squamous cell carcinoma, 31 cases of adenocarcinoma and 15 cases of large cell undifferentiated carcinoma) and 21 samples of same normal lung tissue were randomly selected. Expressions of pULK and PI3KC3 in lung tissues were assessed by immunohistochemistry and Western blot. All dates were analyzed using SPSS13.0 statistical pack?age. Results Immunohistochemistry indicated that pULK and PI3KC3 localized into the cytoplasm. The expression levels of pULK and PI3KC3 are significantly lower in patient with NSCLC than those in peri-tumor tissue (35.1%vs 81.0%, 40.3%vs 76.2%respectively, P<0.01) . Immunohistochemistry and Western bolt analysis confirmed that pULK and PI3KC3 ex?pressions were significantly down-regulated (P<0.01) in patients with low grade cellular differentiation, metastasis of lymph node, or stageⅢandⅣ. And expression levels of pULK and PI3KC3 in NSCLC did not differ significantly with ages, gen?der, tumor size and pathological type. Correlation analysis showed that the expression of PI3KC3 was positively correlated with pULK. Conclusion pULK and PI3KC3 expressions were lower in NSCLC than those in normal lung tissue group. The expression levels of pULK and PI3KC3 in NSCLC were correlated with patient's clinical stage, differentiation grade, lymph node metastasis but were unrelated with age, gender, histological type and size.

Detection of human cytomegalovirus UL97 gene mutations conferring ganciclovir resistance / 中华检验医学杂志

Objective To explore human cytomegalovirus UL97 mutations related to ganciclovir resistance in hematopoietic stem cell transplant (HSCT) recipients.Methods A total of 43 patients,including 24 males and 19 females,with an average age of 21 years old,who had HCMV DNAemia for more than two weeks after HSCT between 2008 and 2010 in Peking University People's Hospital,were included in this prospective study.UL97 GCV resistance mutations were investigated in 49 plasma specimens collected from those patients.GCV resistance mutations such as UL97 M460V/I,H520Q,A591V,A594V,L595S/F,and C603W,were analyzed by modified PCR-RFLP methods.UL97 mutations related to GCV resistance were assayed by the method of PCR-direct sequencing (PCR-DS).An amplified refractory mutation system real-time PCR (ARMS RT-PCR) was developed for the detection of UL97 A594V mutation.Results Eight known UL97 ganciclovir resistance mutations were not detected by PCR-RFLP and PCR-DS.Four new UL97 mutations like UL97 R494P,T502A,N558D,and G561S,were detected by PCR-DS.The ARMS RT-PCR for detecting of UL97 A594V was established successfully.The lower limit of detection of the method was at least 7.5 × 102 copies/ml combined with the use of nucleic acid extraction reagent.UL97 A594V resistance mutation was identified by the method of ARMS RT-PCR in two HSCT recipients.The rate of UL97 A594V mutation was 4.7％ (2/43) in HSCT recipients.Conclusion The ARMS RT-PCR assay represented a sensitive method for the identification of UL97 A594V mutation.