Clinical characteristics and genetic analysis of three children with Congenital chlorine diarrhea / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis for three children with Congenital chlorine diarrhea (CCD).@*METHODS@#Three children with CCD who attended the Affiliated Children's Hospital of Capital Pediatric Institute from June 2014 to August 2020 were selected as the research subjects. Peripheral blood samples of the three children and their parents were collected for genetic testing. And the results were verified by Sanger sequencing.@*RESULTS@#The clinical manifestations of the three children have included recurrent diarrhea, with various degrees of hypochloremia, hypokalemia and refractory metabolic alkalosis. Genetic testing revealed that the three children have all carried variants of the SLC26A3 gene, including homozygous c.1631T>A (p.I544N) variants, c.2063_1G>T and c.1039G>A (p.A347T) compound heterozygous variants, and c.270_271insAA(p.G91kfs*3) and c.2063_1G>T compound heterozygous variants. Sanger sequencing confirmed that all of the variants were inherited from their parents.@*CONCLUSION@#The variants of the SLC26A3 gene probably underlay the CCD in these children. Above finding has enriched the spectrum of SLC26A3 gene variants.

Hypoglycemia caused by AKT2 gene mutation:a case report and literature review / 中华全科医师杂志

A 15-month-old baby girl presenting with hypoglycemia was admitted in Children′s Hospital of Capital Institute of Pediatrics in October 2019. The blood glucose level was 2.4 mmol/L at admission, she showed asymmetry of left and right limbs. The levels of D-3-hydroxybutyric acid, urinary ketone body and free fatty acid were all decreased during hypoglycemia attack, the hyperglycemic hormone was increased, but insulin level was<0.2 μIU/ml. The whole exon gene testing showed that the patient had heterozygous mutation of AKT2 gene c.49G>A (p.E17K), which was mosaicism; then the patients was diagnosed as hypoinsulinemic hypoketotic hypo-fatty-acidemic hypoglycemia due to mutation of AKT2 gene. Blood glucose levels were dynamically monitored, high carbohydrate diet was administered and raw corn starch supplementation was given before bedtime. After 18 months of treatment, the growth and development of the patient was normal, the frequency of hypoglycemia attacks decreased, and bilateral limb asymmetry improved. The relevant literature was searched from Wanfang Database, CNKI and PubMed from January 1980 to March 2021 by using search term"hypoglycemia"and"AKT2 gene". Five cases of hypoglycemia caused by AKT2 mutation were retrieved, all were reported from other countries, no one case from China. The clinical manifestation of this disease is similar to hyperinsulinemic hypoglycemia, but insulin could not be detected during the attack of hypoglycemia, and the patients may have hemihypertrophy. The study suggests that if the patient has hypoglycemia accompanied by hypoinsulinemia and hemihypertrophy, we should consider the possibility of AKT2 gene mutation, and genetic testing should be recommended.

Analysis of clinical features and genetic variants among 12 children with Gitelman syndrome / 中华医学遗传学杂志

OBJECTIVE@#To summarize clinical manifestations and results of genetic testing in 12 children with Gitelman syndrome (GS).@*METHODS@#Clinical data of the children was collected. Whole exome sequencing(WES) was carried out to screen potential variants of genomic DNA. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The patients have included 10 boys and 2 girls, whom were diagnosed at between 2.8 to 15.0 year old. Six patients were due to infections, 5 were due to short stature, and 1 was due to lower limb weakness. All patients were found to carry variants of SLC12A3 gene, which included 11 with compound heterozygous variants and 1 with homozygous variant. All of the 19 alleles of the SLC12A3 gene carried by the patients were delineated, which included 15 missense variants, 2 frameshift variants and 2 splice region variants. These variants were unreported previously, which included c.578_582dupCCACC (p.Asn195Profs*109), c.251C>T (p.Pro84Leu) and c.2843G>A (p.Trp948X).@*CONCLUSION@#The clinical symptoms of GS in children are atypical and often seen in older children. For children with occasional hypokalemia associated with growth failure, GS should be suspected. The majority of GS children carry two pathogenic variants of the SLC12A3 gene, mainly compound heterozygotes, among which p.Thr60Met is the most common one. The discovery of new variants has enriched the spectrum of SLC12A3 gene variants.

Clinical and genetic analysis of a child with neonatal severe parathyroidism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with neonatal severe hyperparathyroidism.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Whole exome sequencing was carried out to screen potential mutations. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry compound heterozygous variants c.179G>A (p.Cys60Tyr) and c.1525G>A (p.Gly509Arg) of the CaSR gene. The c.179G>A variant was derived from her mother and was unreported previously. The c.1525G>A variant was derived from her father and known to be pathogenic.@*CONCLUSION@#The compound heterozygous variants of c.179G>A and c.1525G>A of the CaSR gene probably underlie the disease in the patient. The results of genetic testing has enabled diagnosis and genetic counseling for her family.

Homozygous ectonucleotide pyrophosphatase/phosphodiesterase 1 variants in a girl with hypophosphatemic rickets and literature review / 中华儿科杂志

Objective@#To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants.@*Method@#The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed.@*Result@#Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients.@*Conclusion@#ENPP1 gene mutation was a cause of patient with hypophosphatemic rickets. Comorbid features included generalized arterial calcification of infancy, early onset hearing loss, pseudoxanthoma and ossification of posterior longitudinal ligament. ENPP1 gene testing should be performed on hypophosphatemic rickets patients without PHEX gene variants. Long-term follow up is recommended. The most common types of ENPP1 gene variants were nonsense/splicing variants. The gene c.783C>G was the most common variants in Chinese patients.

Siblings with congenital adrenal cortex hyperplasia (17-α-hydroxylase deficiency) and literature review / 临床儿科杂志

Objective To report clinical characteristics and genetic results of two sisters suffered from congenital adrenal cortex hyperplasia (17-α-hydroxylase deficiency), and relevant literatures were reviewed. Methods Clinical manifestation and laboratory examination data of two sister cases of 17-α-hydroxylase deficiency enrolled in Capital Institute of Pediatrics in March 2016 were analyzed. Sanger sequencing and MLPA for CYP17A1 genes were performed and the parents' genes were also verified. Results The two patients were four years and 10 years old, both suffered from hypokalemia after infections, and hypergonadotrophin gonad hypofunction. One case was with slightly high blood pressure. Laboratory test results showed potassium fluctuation tendency in 1.9~4.0 mmol/L, 17-OHP and DHEA was decreased. Enhanced CT showed different degree of adrenal gland enlargement. Chromosome examination of the older sister is 46, XY. Both sisters demonstrated heterozygous mutation of CYP17A1 gene. The molecular genetic analysis suggested a c.985_987delTACinsAA from father and a deletion spanning exons 1-7 of the CYP17A1 gene from mother. Conclusion 17-α-hydroxylase enzyme deficiency can be diagnosed before adolescence. Clinical hypokalemia with unknown reason and high blood pressure may indicate the disease. The diagnosis can be confirmed with gene sequencing of CYP17A1.

Establishment and evaluation of a rat model of acute radioation-induced liver injury / 中国实验动物学报

@#Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

MRI features of placenta accreta / 中华放射学杂志

ObjectiveTo investigate the MRI features of placenta accreta.MethodsFrom Apr 2009 to Jun 2011,15 patients with placenta accrete received MRI examination.In them,placenta accrcta was diagnosed based on clinical manifestations or postoperative histopathologv.The MR features of placenta accreta in thcm( study group) were retrospectively analyzed and compared with those in 15 pregnant women without placenta accreta (control group)with Fisher exact test.ResultsIn the 15 patients with placenta accreta,uterine bulging and(or) a focal outward contour bulge was detected in 14 patients; heterogeneous signal intensity in the placenta was detected in 15 patients; dark intraplacental bands on T2-weighted images was detected in 15 patients; and increased subplacental vascularity was detected in 11 patients on T1- weighted images.In the study group,14 patients showed at least three of the above four features,and in all of them uterine bulging and(or) a focal outward contour bulge,heterogeneous signal intensity in the placenta and dark intraplacental bands on T2-weighted images were detected; one patient showed heterogeneous signal intensity in the placenta,dark intraplacental bands on T2-weighted images and increased subplacental vascularity.In the control group,none patient had three of the above features.Uterine bulging and(or) a focal outward contour bulge,heterogeneous signal intensity in the placenta,dark intraplacental bands on T2-weighted images and increased subplacental vascularity were detected in 3,6,3 and 4 patients (P=0.000,0.001,0.000 and 0.027 ),respectively.ConclusionsThe main MRI features of placenta accreta are uterine bulging and(or) a focal outward contour bulge,heterogeneous signal intensity in the placenta and dark intraplacental bands on T2-weighted images Besides,increased subplacental vascularity also could provide useful information for the diagnosis of placenta accreta.

Value of Steel Wire Implantation with Prone Table Stereotactic Digital Mammography in the Detection of Microcalcification of the Breast / 中国肿瘤临床

Objective:To explore the clinical value of stereotactic wire-localized biopsy(SWLB)in digital mammography in the detection of microcalcification of the breast.Methods:A total of 45 patients with nonpalpable breast lesions which were positive for microcalcification by mammography but could not be detected clinically underwent SWLB.Their mammography fndings were analyzed in detail with pathology.Results:Among the 45 cases,13 cases(28.9%)had malignant lesions including ductal carcinoma in situ in 3 cases (20.1%),ductal carcinoma in situ with microinvasion in 4 cases(30.8%),invasive ductal carcinoma in 5 cases (38.5%)and intraductal papillary carcinoma in 1 case(7.7%).Thirty-two cases(71.1%)had benign lesions,2 cases(6.3%)of which were severe atypical hyperplasia.Conclusion:SWLB can accurately guide the surgical excision of nonpalpable breast microcalcification lesions and diagnose microcalcifications exactly,which is helpful for increasing the detection rate of eady-stage breast cancer.

Etiological study of hand,foot and mouth disease among children in Shanghai and neighbor areAfls in 2008 / 中华传染病杂志

Objective To investigate the distribution and genetic characteristic of etiological agents among children with hand,foot and mouth disease(HFMD)in Shanghai and neighbor areas in 2008.Methods Throat swabs were collected from the inpatients with HFMD from May to June 2008 in Pediatrics Hospital affiliated to Fudan University,Shanghai,and Deqing,Zhejiang Province.Cerebral spinal fluid(CSF)from some patients were collected as well.Vero,MRC-5 and RD ceils were used to isolate the possible pathogens by observing cytopathic effect(CPE).Enterovirus genus,Coxsaekie virus group A type 16(CoxA16)and enterovirus type 71(EV71)were detected by reverse transcriptase-polymerase chain reaction(RT-PCR),and finally identified by sequencing.Results A total of 107 swabs and 22 CSF samples were collected from all 100 inpatients.Swabs of 50 children caused CPE observed.Among them,enteroviruses accounted for 74.0%(37/50),which including 26 (52.0%)of EV71,10(20%)of CoxAl6 and 1(2.0%)of CoxB3,and 13(26.0%)of other pathogens.All the 26 EV71 strains were similar with the isolates from Zhejiang Province and Fuyang,Anhui Province in 2008,which belonged tO genotype Cl all the 10 CoxAl6 strains belonged to genetic lineages C.Conclusions The causative agents of HFMD are complicated.CoxA16 and EV71 are predominant among children with HFMD in Shanghai and neighbor areas in 2008,while the pathogens of some patients are still unknown.

The histological underestimation of stereotactic core needle biopsy in breast lesions / 中华放射学杂志

Objective To analyze the histological underestimation of stereotactic core needle biopsy (SNCB).and tO attract clinicians' attention.Methods SNCB was performed in 146 patients with 179 lesions from September 2000 to June 2005.and 21 lesions were underestimated histologically.0f 21 nonpalpable breast lesions(NPBL).6 lesions were diagnosed as BI-RADS nl,12 8S BI-RADS Ⅳ,3 as BI-RADS V according to BI-RADS before biopsy.Mammography showed 16 lesions with calicification, 2 cases with masses,1 case with asymmetry density and 2 cases with stellate sign.Results Eleven lesions diagnosed as fibrocystic disease with atypical ductal hyperplasia by biopsy were proved to be ductal carcinoma in situ (DCIS)in 7 lesions and early infiltration in 4 lesions by pathology.3 lesions diagnosed as severe atypical hyperplasia by biopsy were finally proved to be 1 carcinoma in situ and early infiltration in 2 lesions by pathology.3 lesions diagnosed as DCIS by biopsy were invasive carcinoma.4 lesions diagnosed papillary lesions by biopsy and finally were 1 carcinoma in situ,1 early infiltration,1 infiltrating ductal carcinoma and l intraductal papillary adenocarcinoma.Conclusion The histological underestimation of SCNB Was related to the stereotactic location technology,lesion and doctor'S understanding,the radiologist should master the biopsy skills.

Application of diffusion weighted echo-planar MR imaging in head and neck lesions / 中华放射学杂志

Objective to investigate the value of diffusion-weighted echo-planar MR imaging in the diagnosis of head and neck lesions.Methods Fifty-seven patients with 85 head and neck lesions were enrolled in the study,including 22 patients with 22 malignant tumors,13 patients with 13 benign tumors, 13 patients with 17 cystic and liquefactive lesions(including 8 patients with 12 cystic lesions,4 patients with 4 tumor necrosis,1 patients with 1 abcess)and 33 lymph nodes.The lesions were all confirmed by operation and clinical follow up.Echo-planar difffusion-weighted imaging (DWI)was performed with different b values (0,500,and 1,000s?mm~(-2)),and the apparent diffusion coefficients (ADCs)were measured.Results Malignant and benign tumors had different characteristics in DWI with different b values.With the increase of b value,the signal intensity of tumor/spinal cord ratio decreased quickly in DWI in benign tumors,while the signal intensity of tumor/spinal cord ratio remained similar in DWI in malignant tumors.The mean ADC value of'malignant tumors[(0.78?0.24)?10~(-3)mm~2? s~(-1)] was significantly lower than that of benign tumors [(1.48?+0.20)?10~(-3)mm~2?s~(-1)] (t = 8.9,P