Clinical and genetic analysis of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH).@*METHODS@#Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated.@*RESULTS@#Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting).@*CONCLUSION@#The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.

Imaging Characteristics of 68Ga-DOTATATE PET/CT in Tumor-Induced Osteomalacia / 罕见病研究

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23) that promotes urinary phosphorus excretion. Thus, TIO is typically characterized by phosphoruria, hypophosphatemia, and osteomalacia. Diagnosis and localization of the tumor is often difficult due to its small size, slow growth and concealed location. Due to the high expression of somatostatin receptors in pathogenic tumors, nuclear medicine functional imaging, particularly somatostatin receptor imaging, is used for diagnosis and localization of culprit tumors with high sensitivity and specificity. Here we retrospectively analyze 25 cases in which 68Ga-DOTATATE PET/CT successfully localized and diagnosed TIO culprit tumors. The clinical features, pathological results and image characteristics of 68Ga-DOTATATE PET/CT imaging were analyzed and compared with other imaging diagnostic techniques. It was confirmed that 68Ga-DOTATATE PET/CT imaging was the preferred imaging technique for successful diagnosis and localization of TIO pathogenic tumors.

Mechanism research status of daidzein in the prevention and treatment of osteoporosis through estrogen-like effect / 中国药房

Osteoporosis， as a systemic bone disease with high incidence rate and high disability rate， has become a research hotspot in recent years. The daidzein in soybean isoflavones can bind with estrogen receptors， simulating the prevention and treatment of osteoporosis with estrogen-like effect. Its mechanism of action includes promoting osteoblast formation and differentiation by activating the Wnt signaling pathway， increasing bone density， and improving bone tissue health； inhibiting osteoclast differentiation and slowing down bone resorption by reducing receptor activator of nuclear factors κB ligand/ osteoprotegerin ratio， downregulating the expression of macrophage colony-stimulating factor （M-CSF）； collaborating antioxidant and immune regulation to achieve the goal of preventing and treating osteoporosis. In addition， different doses of daidzein have different effects on bone density and osteoporosis， which may be related to factors such as study design， sample selection， and individual differences.

Dynamic phenotype of lung type Ⅱ alveolar epithelial cells in radiation-induced lung injury and its role in the formation of fibrosis / 中华放射医学与防护杂志

Objective:To explore the dynamic phenotype of type Ⅱ alveolar epithelial cells(AEC Ⅱ)in radiation-induced lung fibrosisand its role in the formation of fibrosis.Methods:Totally 90 C57BL/6J female mice were divided into 2 groups: irradiation group (50, thoracic irradiation with a single dose of 20 Gy X-rays), control group (40, sham irradiation). At 24 h, 4 and 12 weeks after irradiation, 5 mice were euthanized and the lungs were collected for pathological observation. The other lungtissues were collected for the isolation of primary AEC Ⅱ cells with microbeadssorting.The mRNA expressions of proSP-C, HOPX, vimentin, β-catenin and TGF-β1 in AEC II cells were detected by RT-PCR.Results:Acute pneumonitis was observed in the lungs at 24 h after irradiation and alleviated in accompany with partial alveolar septal thickening and a small amount of collagen deposition at 4 weeks after irradiation. The collagen deposition became more pronounced at 12 weeks after irradiation, together with collapsed and fused alveolar cavities, alveolar septal hyperplasia, and pulmonary fibrosis formation.The mRNAexpression levels of proSP-C and HOPX in primary AEC Ⅱ cells increased at 24 hours after irradiation and then approached to a peak value at 4 weeks after irradiation ( F=8.441, 3.586, P=0.036). The mRNA expression levels of vimentin, a biomarker of EMT, was increased significantly at 4 weeks and continued up to 12 weeks after irradiation( F=8.358, P=0.001). The mRNA expression levels of profibrotic factors β-catenin and TGF-β1 were both significant increased at 12 weeks after irradiation( F=4.62, 3.279, P=0.044). Conclusions:The phenotypeof AECⅡ cells could not only be transformed from proSP-C+ to HOPX+ /proSP-C+ , HOPX+ /proSP-C+ /vimentin+ , and vimentin+ /proSP-C, but also differentiated into mesenchymal cells with highly expressed profibrotic factors, thereby inducing EMT process, which either played a role in the repair of radiation-induced lung injury or triggered radiation-induced fibrosis.

Spatio-temporal aggregation of hemorrhagic fever with renal syndrome in Shandong Province from 2017 to 2020 / 中华地方病学杂志

Objective:To study the epidemiological characteristics and spatio-temporal aggregation of hemorrhagic fever with renal syndrome (HFRS) in Shandong Province, and to provide reference for formulating reasonable prevention and control strategies.Methods:Retrospective analysis was used to collect HFRS surveillance data and confirmed case data in Shandong Province from 2017 to 2020 in the "China Disease Prevention and Control Information System Infectious Disease Surveillance System". Geoda 1.18 software was used for global and local spatial autocorrelation analysis, SaTScan 9.6 software was used for spatio-temporal scanning analysis, and ArcGis 10.7 software was used for map drawing and visual display.Results:A total of 3 753 cases of HFRS were reported in Shandong Province from 2017 to 2020, including 56 deaths. The annual incidence rate was 1.26/100 000, 1.22/100 000, 0.75/100 000 and 0.53/100 000, respectively, with an average annual incidence rate of 0.94/100 000. The incidence of HFRS was obviously seasonal, mainly concentrated in autumn and winter from October to December, accounting for 50.41% (1 892/3 753). The age of onset was mainly 30-59 years old, accounting for 61.68% (2 315/3 753). The male to female ratio was 2.76 ∶ 1.00 (2 756 ∶ 997). The occupation distribution was mainly farmers, accounting for 81.99% (3 077/3 753). The global spatial autocorrelation analysis showed that HFRS showed spatial aggregation areas in each year from 2017 to 2020 (Moran' I = 0.38, 0.33, 0.59, 0.46, Z = 7.47, 7.23, 10.69, 8.66, P < 0.001). The local spatial autocorrelation analysis showed that "high-high" aggregation areas were mainly concentrated in central and southeast of Shandong Province, while "low-low" aggregation areas were mainly concentrated in northwest of Shandong Province. Spatio-temporal scanning analysis revealed 1 type Ⅰ agglomerations and 2 type Ⅱ aggregation areas. The type Ⅰ aggregation areas occurred from October to November 2018, covering 22 counties (districts) of 5 cities in Qingdao, Yantai, Weifang, Weihai and Rizhao. The first type Ⅱ aggregation area occurred from October to November 2017, involving 23 counties (districts) of 8 cities in Jinan, Zibo, Zaozhuang, Weifang, Jining, Tai 'an, Rizhao and Linyi. The second type Ⅱ aggregation area occurred in Jinxiang County, Jining City from February to March 2017. Conclusion:The incidence of HFRS in Shandong Province from 2017 to 2020 has obvious spatio-temporal aggregation, and the hot spots are concentrated in central and southeast of Shandong Province, which should be regarded as a key area for prevention and control of HFRS.

Genetic analysis of 21 fetuses with high suspicion of congenital skeletal malformation by prenatal ultrasound / 中华围产医学杂志

Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.

Prevalence of depressive symptoms among community-dwelling elderly with mild cognitive impairment in China: a Meta-analysis / 中华全科医师杂志

Objective:To estimate the prevalence of depressive symptoms in community-dwelling elderly with mild cognitive impairment(MCI) in China by systemic review.Methods:PubMed, Web of Science, CNKI, VIP database and other databases were searched for cross-sectional studies on the prevalence of depressive symptoms in the elderly with MCI in China. The search period was from January 1, 2011 to October 1, 2021. The studies were screened according to predefined inclusion and exclusion criteria. Stata 12.0 software was used for statistical analysis, and finally the prevalence rate of depressive symptoms in the elderly with MCI in China was calculated.Results:A total of 2 036 relevant studies were retrieved, among which 14 met the inclusion criteria, involving 3 819 cases. Meta-analysis showed that 32.3%(30.9%-33.7%) of community-dwelling elderly with MCI had depressive symptoms. Subgroup analysis showed that the detection rate of depressive symptoms in studies published during 2016—2021 was higher than that during 2011—2015 (34.6% vs. 23.5%, χ2=11.64, P<0.001).However there were no significant differences in detection rate between genders, among studies using different depression assessment and MCI assessment tools, and among different geographic regions (all P>0.05). Conclusion:The study shows that the prevalence of depressive symptoms in community-dwelling elderly with MCI in China is high and it presents a rising trend, suggesting that attention should be paid to mental health of elderly in the community and the screening of depressive symptoms should be strengthened for those with MCI.

Analysis of the short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy / 中华核医学与分子影像杂志

Objective:To analyze the influencing factors of short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy (RESCC). Methods:From January 2013 to March 2019, 47 patients (42 males, 5 females; age: 47-77 years) with RESCC who underwent CT guided 125I seed implantation in Hebei General Hospital were retrospectively analyzed. Patients were divided into effective group (complete remission (CR)+ partial remission (PR)) and ineffective group (stable disease (SD)+ progressive disease (PD)) according to response evaluation criteria in solid tumors (RECIST) at 3 months after implantation. Multivariate logistic regression was used to analyze the independent influencing factors of short-term efficacy. Cut-off values were determined by ROC curve. Results:Of 47 patients, 26 were effective (3 were CR and 23 were PR) and 21 were ineffective (7 were SD, 14 were PD). Multivariate regression analysis showed that tumor diameter, immediate postoperative dose delivered to 90% gross tumor volume ( D90), recurrence interval time were independent influencing factors of short-term efficacy (odds ratio ( OR; 95% CI): 4.240(1.220-14.737), 0.999(0.999-1.000), 0.989(0.979-1.000), Wald values: 5.163, 5.043, 3.956, all P<0.05). ROC curve showed that the AUC of tumor diameter, D90 and recurrence interval time were 0.782, 0.786 and 0.838 respectively, with cut-off values of 4.85 cm, 115.78 Gy and 297.5 d respectively. Conclusions:The short-term efficacy of 125I seed implantation for RESCC is mainly related to the tumor diameter, immediate postoperative D90 and recurrence interval time. Patients with tumor diameter <4.85 cm, immediate postoperative D90>115.78 Gy and recurrence interval time >297.5 d have better efficacy.

Identification and analysis of anovel variant of TRAPPC2 in a X-linked spondyloepiphyseal dysplasia tarda pedigree / 中华骨科杂志

Objective:To provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.

Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and genetic variant in a patient with Usher syndrome.@*METHODS@#Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.@*RESULTS@#The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.@*CONCLUSION@#The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.

Analysis of a Chinese pedigree affected with dyschromatosis symmetrica hereditaria due to a novel variant of ADAR gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.@*RESULTS@#The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.@*CONCLUSION@#The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.

Whole-genome sequencing of SARS-CoV-2 Gamma variant first discovered in Chinese mainland / 中华微生物学和免疫学杂志

Objective:To investigate the whole genome of SARS-CoV-2 causing COVID-19 in Rongcheng city of Shandong Province in May 2022 and to further analyze the nucleotide and amino acid variations for source tracing.Methods:High-throughput sequencing was used to sequence the SARS-CoV-2 genome in 15 nasopharyngeal swab samples from COVID-19 cluster infections and three environmental samples related to an aquatic product import company. Whole-genome sequence splicing, variant site analysis and sequence typing were performed on the raw sequencing data using virus sequence and variant analysis software. A phylogenetic tree was constructed by evolutionary analysis software. Epidemiological investigation was used to trace the potential source of infection.Results:Thirteen whole genome sequences of SARS-CoV-2 with the length ranging from 29 653 bp to 29 780 bp were successfully obtained from the nasopharyngeal swab samples. The average sequencing depth was 1 756-6 565 X and the genome coverage was 99.20%-99.63%. The results of Pangolin typing showed that the 13 genomes belonged to the VOC/Gamma (P.1.15) evolutionary branch. Compared with the Wuhan reference strain (NC_045512.2), the 13 genome sequences had 40-41 nucleotide mutation sites. There were 23-24 amino acid variation sites in seven protein domains (ORF1a, ORF1b, S, ORF3a, ORF8, ORF9b and N proteins). Evolutionary analysis showed that the viral sequence was grouped to the same subclade as the reference strain from Argentina (EPI_ISL_4082233).Conclusions:In this study, the whole genome sequences of 13 Gamma variant strains were obtained from COVID-19 cluster infections associated with imported cold-chain aquatic products in Rongcheng city, and the imported seafood from South America in 2021 was found to be the source of the virus in a timely manner. This study provided reference for the SARS-CoV-2 variant analysis and case tracing and also suggested that the survival and transmission ability of SARS-CoV-2 on the surface of cold-chain products should not be underestimated and needed further investigation.

Dermoscopic features of 266 cases of melanonychia / 中华皮肤科杂志

Objective:To investigate dermoscopic manifestations and features of melanonychia.Methods:A retrospective analysis was carried out on dermoscopic images of 4 common types of melanonychia collected in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2016 to July 2020.Results:A total of 266 cases of melanonychia were collected, including 64 (24.1%) of subungual melanoma, 52 (19.5%) of nail matrix nevi, 89 (33.5%) of subungual hemorrhage, and 61 (22.9%) of onychomycosis. Subungual melanoma and nail matrix nevi mostly occurred in the fingernails. To be specific, subungual melanoma most frequently occurred in the thumbnails (62.8%) , while nail matrix nevi mostly involved the 2 nd - 5 th fingernails (73.9%) . Subungual hemorrhage and onychomycosis mostly occurred in the toenails, and there were 51 (57.3%) cases of subungual hemorrhage of the toenails and 46 (75.4%) cases of onychomycosis of the toenails. Subungual melanoma mostly occurred in patients aged over 40 years (49 cases, 76.8%) , while the other 3 types of melanonychia mostly affected patients aged under 40 years. Dermoscopic manifestations of subungual melanoma mainly included regular longitudinal bands (35 cases, 54.7%) or irregular bands (25 cases, 39.0%) whose width was greater than 3 mm in 87.5% cases, Hutchinson sign (36 cases, 56.3%) , and ruptures (15 cases, 23.4%) which mainly were black-brown in color; dermoscopic manifestations of nail matrix nevi mainly were a single regular pigmented band (52 cases, 100%) whose width was less than 3 mm in 36 (69.2%) cases, and Hutchinson sign (26 cases, 50%) , while no ruptures were observed in nail matrix nevus lesions; subungual hemorrhage dermoscopically manifested as diffuse macules (74 cases, 83.1%) , and globular dark red or black hemorrhagic structures were observed in 85 (95.5%) cases; fungal melanonychia was dermoscopically characterized by irregular dark brown longitudinal bands (54 cases, 88.5%) . Conclusions:Subungual melanoma was dermoscopically characterized by regular longitudinal bands with a width of greater than 3 mm, nail matrix nevi by regular longitudinal bands, subungual hemorrhage by diffuse macules, and onychomycosis by irregular longitudinal bands. Dermatoscopy can be used to identify melanonychia lesions and provide a basis for auxiliary diagnosis of subungual melanoma.

Comparison study of left ventricular reverse remodeling after transcatheter aortic valve replacement of bicuspid versus tricuspid aortic valve stenosis / 中华超声影像学杂志

Objective:To compare the left ventricular (LV) reverse remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) stenosis and tricuspid aortic valve (TAV) stenosis.Methods:The data of patients who underwent TAVR procedure from March 2013 to December 2018 in the Second Affiliated Hospital of Zhejiang University were retrospectively reviewed. The patients were divided into BAV group and TAV group according to cardiac computed tomography. Echocardiographic parameters, including aortic valve peak velocity (Vmax), mean gradient (PGmean), effective orifice area(EOA), interventricular septum diastolic thickness (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), left ventricular end diastolic diameter( LVEDd), LV mass index (LVMI), ΔLVMI%, left ventricular ejection fraction( LVEF) of the two groups at baseline, 1 week, 1 month and 1 year post TAVR procedure were obtained and compared.Results:①Compared with preoperative measurements, both groups showed decreases in Vmax, PGmean and increase in EOA at 1 week, 1 month, 1 year follow-ups(all P<0.05). No significant differences were found in Vmax, PGmean, EOA, moderate/sever perivalvular leakage(PVL), moderate/sever prosthetic-patient mismatch(PPM) between BAV group and TAV group at 1 year. ②Both groups showed decreases in IVSd, LVPWd, LVEDd at 1 month, 1 year post TAVR compared with those before the procedure (all P<0.05), as well as increases in LVEF at 1 week, 1 month, 1 year (all P<0.05). Downward trends of LVMI were detected in both groups within 1 year follow-up( P<0.05). ③Compared to TAV group, BAV group showed smaller baseline LVMI( P<0.05), while there were no significant differences in ΔLVMI% post TAVR for all follow-up times of the two groups(all P>0.05). Repeated measures analysis of variance also showed no significant differences in downward trend of LVMI between the two groups after TAVR within 1 year( P>0.05). Conclusions:Left ventricular reverse remodeling can be detected in both BAV and TAV patients after TAVR, which starts from 1 week and can be lasted for 1 year post procedure. Patients with bicuspid morphology might experience similar reverse LV remodeling post TAVR versus patients with tricuspid morphology.

Genotypic and phenotypic analysis of RHO gene variants in a Chinese Han autosomal dominant retinitis pigmentosa family / 中华实验眼科杂志

Objective:To analyze the pathogenic genes and clinical phenotypes of a Chinese Han family with autosomal dominant retinitis pigmentosa (ADRP).Methods:A pedigree investigation study was conducted, and a Chinese Han RP family that underwent genetic counseling in the Henan Provincial People's Hospital in November 2019 was collected.Twenty members of this family from 4 generations, including 9 patients and 11 phenotypically normal individuals, were enrolled.Visual acuity, peripheral visual field test and fundus examination were performed on some family members.Peripheral blood samples were collected from the family members, and DNA was extracted.Exon-targeted sequencing containing 43 genes associated with RP was performed on the proband using the Ion Torrent PGM sequencing platform.The mutations were verified by polymerase chain reaction and Sanger sequencing.Online software was applied to predict the protein function of the variant.The amino acid sequences of the variant loci were compared using the ClustalW2 multiplex alignment program.The pathogenicity of the variant was analyzed according to American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variant.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2019[15]).Results:The family was consistent with autosomal dominant inheritance.The proband, a 26-year-old male, had bilateral night blindness since childhood, with visual acuity of 0.25 in the right eye and 0.5 in the left eye.There was osteoblast-like pigmentation in his both retinas, thinned retinal vessels and pale optic disc.Full-field electroretinogram examination showed reduced scotopic a- and b-wave peaks and severely reduced photopic a- and b-wave peaks.The rest of the family began to develop night blindness when 7 to 10 years old, having complete loss of peripheral vision around 50 years of age, and typical RP changes were found in ophthalmic examination.Genetic testing revealed a heterozygous missense variant c. 982delC (p.L328fs) in exon 5 of the family's rhodopsin ( RHO) gene (NM_000539.3). This variant resulted in the change of 21 amino acids after amino acid 328 in the encoded RHO protein, increasing amino acids in the coding region from 348 to 358 and altering the structure of the RHO protein.The analysis of protein homology sequence alignment between several different species showed that the locus was highly conserved.According to the guidelines of the ACMG criteria and guidelines for classification of genetic variants, the variant was a pathogenic mutation because there were six evidences including one very strong evidence of pathogenicity PVS1, two moderate evidences of pathogenicity PM2 and three supporting evidences of pathogenicity, PP1, PP3 and PP4. Conclusions:The c. 982delC variant in the RHO gene is a pathogenic mutation in this pedigree, and this variant is reported for the first time in a Chinese Han family.

Combined application of DOPS and Mini-CEX in clinical skill evaluation / 中华医学教育探索杂志

Clinical skills training is an important part of medical students' training, which requires the selection of appropriate evaluation tools. At present, the direct observation of procedural skills (DOPS) and mini clinical evaluation exercise (Mini-CEX) are widely used, however, it is not comprehensive to use only one of the tools for evaluation. Based on the application situation of DOPS and Mini-CEX in clinical skill assessment at home and abroad, this paper will elaborate the combined application of DOPS and Mini-CEX in clinical teaching and standardized residency training for resident physicians, so as to make more comprehensive and systematic evaluation.

Clinical characteristics and pathogenic gene analysis in a large pedigree with multiple epiphyseal dysplasia / 中华骨科杂志

Objective@#To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients).@*Methods@#The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing.@*Results@#The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree.@*Conclusion@#A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.

Genetic analysis of a patient with late infantile metachromatic leukodystrophy / 中华医学遗传学杂志

OBJECTIVE@#To detect variants of ARSA gene in a child featuring late infantile metachromatic leukodystrophy (MLD).@*METHODS@#PCR and Sanger sequencing was carried out for the patient and her parents.@*RESULTS@#The patient had typical features of MLD including ARSA deficiency, regression of walking ability, and demyelination. Compound heterozygous variants of the ARSA gene, namely c.960G>A and c.244C>T, were detected in the patient, for which her mother and father were respectively heterozygous carriers. ARSA c.960G>A was known to be pathogenic, while ARSA c.244C>T was a novel variant. The same variants were not detected among 50 healthy controls.@*CONCLUSION@#The compound heterozygous variants c.960G>A and c.244C>T of the ARSA gene probably underlie the MLD in this patient.

Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).@*METHODS@#Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.@*RESULTS@#DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.@*CONCLUSION@#The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.

A case of hyaline fibromatosis syndrome caused by compound heterozygous mutations in the ANTXR2 gene / 中华皮肤科杂志

A female patient aged 7 years and 5 months presented with multiple skin defects of the scalp, ears, hands and in the sacrococcygeal region, and multiple joint flexion contractures of the extremities for more than 7 years. Skin examination showed skin defects of the scalp, auricles, hands and in the sacrococcygeal region, gingival swelling, and multiple joint flexion contractures of the extremities. Genetic testing of the peripheral blood revealed 2 compound heterozygous mutations c.1073delC (A359Lfs*51) and c.1073dupC (A359Cfs*13) in the anthrax toxin receptor-2 ( ANTXR2) gene in the patient, which were inherited from her mother and father respectively. The patient was diagnosed with hyaline fibromatosis syndrome. Surgical treatment was rejected, and anti-inflammatory drugs, analgesics and other drugs were administered for symptomatic treatment. During follow-up of half a year, the child occasionally had mild diarrhea, and other symptoms did not progress markedly.