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1.
Article in Chinese | WPRIM | ID: wpr-1009262

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a Chinese pedigree affected with Alström syndrome.@*METHODS@#A pedigree with 5 members affected with Alström syndrome who had visited the First Affiliated Hospital of Zhengzhou University in February 2021 was selected as the study subject. Clinical data of the pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA. Genetic testing was carried out for the eldest daughter and third son through whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The eldest daughter (14 years old) and the third son (11 years old) both had congenital nystagmus, amblyopia, growth retardation and type 2 diabetes. WES revealed that both had harbored homozygous c.3538A>T (p.Lys1180*) variant of the ALMS1 gene. Sanger sequencing confirmed that the father, mother, and second daughter were all heterozygous carriers. Based on the Guidelines for Genetic Variation and the Technical Standards for Interpretation and Reporting of Primary Copy Number Variations, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The homozygous c.3538A>T (p.Lys1180*) variant of the ALSM1 gene probably underlay the Alström syndrome in this pedigree, which has provided a reference for the clinical treatment.


Subject(s)
Adolescent , Child , Humans , Male , Female , Alstrom Syndrome/genetics , Diabetes Mellitus, Type 2 , DNA Copy Number Variations , East Asian People , Pedigree
2.
Article in Chinese | WPRIM | ID: wpr-1009306

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a fetus with multiple malformations.@*METHODS@#Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#Prenatal ultrasound scan at 21+5 gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c.607C>T (p.Arg203Trp) variant of the ACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing.@*CONCLUSION@#Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c.607C>T (p.Arg203Trp) variant of the PACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.


Subject(s)
Female , Pregnancy , Humans , Prenatal Diagnosis , Ultrasonography, Prenatal , Syndrome , Fetus , Abnormalities, Multiple , Vesicular Transport Proteins
3.
Article in Chinese | WPRIM | ID: wpr-1009318

ABSTRACT

Hereditary bilirubin metabolic disorder is an important cause for jaundice. For its diverse types and similar clinical manifestations, it has been difficult to make a clear etiological diagnosis. The application of next generation sequencing in recent years has delineated the more and more genetic etiologies for jaundice. This article has reviewed the clinical manifestations and genetic etiology of bilirubin metabolic disorder jaundice, with an aim to enhance the understanding of such diseases and facilitate their clinical diagnosis and treatment, which will provide a reference for genetic counseling and/or prenatal diagnosis for the affected individuals and families.


Subject(s)
Female , Pregnancy , Humans , Metabolic Diseases/genetics , Jaundice/genetics , Bilirubin , Genetic Counseling , Phenotype
4.
Article in Chinese | WPRIM | ID: wpr-1029323

ABSTRACT

This article reported the genetic etiology of two pedigrees with Alstrom syndrome and the results of prenatal genetic diagnosis in the second pregnancies of the two pedigrees. The probands in the two pedigrees both had different degrees of visual abnormalities. The mothers of the two probands were pregnant again and received prenatal diagnosis in the First Affiliated Hospital of Zhengzhou University. Whole-exome sequencing and Sanger sequencing confirmed that the proband of pedigree 1 carried compound heterozygous variants of c.6103C>T(p.Gln2035*) and c.6430C>T(p.Arg2144*) in ALMS1 gene, and the parents were carriers. While the proband of pedigree 2 was found to carry compound heterozygous variants of c.9148_9149delCT(p.Cys3051Serfs*9) and c.12028delC(p.Leu4010Typfs*19) in ALMS1 gene and the parents were also carriers. Among these variants, c.6103C>T(p.Gln2035*), c.9148_9149delCT(p.Cys3051Serfs*9) and c.12028delC(p.Leu4010Typfs*19) were all de novo ones. Prenatal genetic detection confirmed the fetus of pedigree 1 carried c.6430C>T(p.Arg2144*) variant inherited from the father and the pregnancy was continued after genetic counselling, while the fetus of pedigree 2 was found to carry both of the same variants as the proband and the pregnancy was terminated.

5.
Chinese Herbal Medicines ; (4): 291-297, 2023.
Article in English | WPRIM | ID: wpr-982496

ABSTRACT

OBJECTIVE@#Flavonoids are the bioactive compounds in safflower (Carthamus tinctorius), in which chalcone synthase (CHS) is the first limiting enzyme. However, it is unclear that which chalcone synthase genes (CHSs) are participated in flavonoids biosynthesis in C. tinctorius. In this study, the CHSs in the molecular characterization and enzyme activities were investigated.@*METHODS@#Putative chalcone biosynthase genes were screened by the full-length transcriptome sequences data in C. tinctorius. Chalcone biosynthase genes in C. tinctorius (CtCHSs) were cloned from cDNA of flowers of C. tinctorius. The cloned gene sequences were analyzed by bioinformatics, and their expression patterns were analyzed by real-time PCR (RT-PCR). The protein of CtCHS in the development of flowers was detected by polyclonal antibody Western blot. A recombinant vector of CtCHS was constructed. The CtCHS recombinant protein was induced and purified to detect the enzyme reaction (catalyzing the reaction of p-coumaryl-CoA and malonyl-CoA to produce naringin chalcone). The reaction product was detected by HPLC and LC-MS.@*RESULTS@#Two full-length CtCHS genes were successfully cloned from the flowers of safflower (CtCHS1 and CtCHS3), with gene lengths of 1525 bp and 1358 bp, respectively. RT-PCR analysis showed that both genes were highly expressed in the flowers, but the expression of CtCHS1 was higher than that of CtCHS3 at each developmental stage of the flowers. WB analysis showed that only CtCHS1 protein could be detected at each developmental stage of the flowers. HPLC and LC-MS analyses showed that CtCHS1 could catalyze the conversion of p-coumaryl-CoA and malonyl-CoA substrates to naringin chalcone.@*CONCLUSION@#CtCHS1 is involved in the biosynthesis of naringin chalcone in safflower.

6.
Chinese Critical Care Medicine ; (12): 615-619, 2023.
Article in Chinese | WPRIM | ID: wpr-982642

ABSTRACT

OBJECTIVE@#To investigate the value of coronary computed tomographic angiography (CCTA)-based fractional flow reserve (CT-FFR) and plaque quantitative analysis in predicting adverse outcomes in patients with non-obstructive coronary heart disease (CAD).@*METHODS@#Clinical data of patients with non-obstructive CAD who underwent CCTA at the Affiliated Hospital of Jiangnan University from March 2014 to March 2018 were retrospectively analyzed and followed up, and the occurrence of major adverse cardiovascular event (MACE) was recorded. The patients were divided into MACE and non-MACE groups according to the occurrence of MACE. The clinical data, CCTA plaque characteristics including plaque length, stenosis degree, minimum lumen area, total plaque volume, non-calcified plaque volume, calcified plaque volume, plaque burden (PB) and remodelling index (RI), and CT-FFR were compared between the two groups. Multivaritate Cox proportional risk model was used to evaluate the relationship between clinical factors, CCTA parameters and MACE. The receiver operator characteristic curve (ROC curve) was used to assess the predictive power of outcome prediction model based on different CCTA parameters.@*RESULTS@#Finally 217 patients were included, of which 43 (19.8%) had MACE and 174 (80.2%) did not. The median follow-up interval was 24 (16, 30) months. The CCTA showed that patients in the MACE group had more severe stenosis than that in the non-MACE group [(44.3±3.8)% vs. (39.5±2.5)%], larger total plaque volume and non-calcified plaque volume [total plaque volume (mm3): 275.1 (197.1, 376.9), non-calcified plaque volume (mm3): 161.5 (114.5, 307.8) vs. 117.9 (77.7, 185.5)], PB and RI were larger [PB: 50.2% (42.1%, 54.8%) vs. 45.1% (38.2%, 51.7%), RI: 1.19 (0.93, 1.29) vs. 1.03 (0.90, 1.22)], CT-FFR value was lower [0.85 (0.80, 0.88) vs. 0.92 (0.87, 0.97)], and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that non-calcified plaques volume [hazard ratio (HR) = 1.005. 95% confidence interval (95%CI) was 1.025-4.866], PB ≥ 50% (HR = 3.146, 95%CI was 1.443-6.906), RI ≥ 1.10 (HR = 2.223, 95%CI was 1.002-1.009) and CT-FFR ≤ 0.87 (HR = 2.615, 95%CI was 1.016-6.732) were independent predictors of MACE (all P < 0.05). The model based on CCTA stenosis degree+CT-FFR+quantitative plaque characteristics (including non-calcified plaque volume, RI, PB) [area under the ROC curve (AUC) = 0.91, 95%CI was 0.87-0.95] had significantly better predictive efficacy for adverse outcomes than the model based on CCTA stenosis degree (AUC = 0.63, 95%CI was 0.54-0.71) and the model based on CCTA stenosis degree+CT-FFR (AUC = 0.71, 95%CI was 0.63-0.79; both P < 0.01).@*CONCLUSIONS@#CT-FFR and plaque quantitative analysis based on CCTA are helpful in predicting adverse outcomes in patients with non-obstructive CAD. Non-calcified plaque volume, RI, PB and CT-FFR are important predictors of MACE. Compared with the prediction model based on stenosis degree and CT-FFR, the combined plaque quantitative index can significantly improve the prediction efficiency of adverse outcomes in patients with non-obstructive CAD.


Subject(s)
Humans , Fractional Flow Reserve, Myocardial , Coronary Angiography/methods , Constriction, Pathologic , Retrospective Studies , ROC Curve , Predictive Value of Tests , Plaque, Atherosclerotic/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Tomography, X-Ray Computed , Coronary Artery Disease/diagnostic imaging
7.
Article in Chinese | WPRIM | ID: wpr-973755

ABSTRACT

ObjectiveTo study the potential quality marker (Q-marker) of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), multivariate statistical analysis (MSA), and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were employed to screen out the main marker components that caused differences between groups. Moreover, network pharmacology technology was applied to predict the potential "sore throat-relieving" components, and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds, including alkaloids, diterpenoid lactones, and sterols, were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA: Columbamine, jatrorrhizine, palmatine, menisperine, and columbin. Network pharmacology analysis yielded six compounds: tetrahydropalmatine, palmatine, menisperine, fibleucin, neoechinulin A, and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6, epidermal growth factor receptor, prostaglandin G/H synthase 2, matrix metalloproteinase-9, proto-oncogene tyrosine-protein kinase Src and other targets, and regulating Hepatitis B, influenza A, human T-cell virus infection, human cytomegalovirus infection, coronavirus disease-2019, and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine, menisperine, and columbin, which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix, which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

8.
Article in Chinese | WPRIM | ID: wpr-928414

ABSTRACT

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with normal ultrasonographic finding at 20 weeks' gestation but a copy number variant(CNV) of 13q indicated by non-invasive prenatal test (NIPT).@*METHODS@#Karyotyping analysis and chromosomal CNV assay were carried out on the amniotic fluid sample. Parental peripheral blood sample was collected for chromosomal analysis. Detailed fetal ultrasound scan was carried out to rule out structural abnormalities of the fetus.@*RESULTS@#The fetus was detected with a heterozygous 10.14 Mb deletion at 13q21.1q21.32, which has originated from the phenotypically normal mother. No apparent karyotypic abnormality was detected in the fetus and its parents. No ultrasonic abnormality was found in the fetus.@*CONCLUSION@#Both the fetus and its mother have carried a heterozygous 10.14 Mb deletion at 13q21.1q21.32 and presented normal phenotypes.Combined with literature review, the segmental deletion was judged to be a benign variant.


Subject(s)
Female , Humans , Pregnancy , Genetic Counseling , Karyotyping , Pedigree , Prenatal Diagnosis , Ultrasonography, Prenatal
9.
Article in Chinese | WPRIM | ID: wpr-907811

ABSTRACT

Objective:To estimate and analyze the occurrence of post-thyroidectomy syndrome (PTS) following endoscopic thyroidectomy via areola approach (ETAA) vs open thyroidectomy (OT) .Methods:Data of 903 consecutive cases, aged from 20 to 66 with 231 males and 672 females, in Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, from Jan. 2016 to Dec. 2017 were analyzed retrospectively. They were enrolled according to the same criteria. Based on different procedures, the cases were divided into ETAA group (n=162) and OT group (n=741) . Intraoperative procedure was according to unified principle. Drainage tube was removed if 24-hour drainage volume was less than 20 ml. Following-up was implemented by telephone or outpatient clinic. Data of 2 groups of 5 PTS items during 1 m, 3 m, 6 m and 1 y postoperatively and the scores of the medical outcomes study short form 36-item health survey (SF-36) V2 were analyzed by independent sample t test and repeated measures analysis of variance. Results:The patients of 2 groups were all followed up for more than 1 y with 43 cases censored (4.8%) . Demographic data of the rest of 2 groups were not different statistically ( P>0.05) . Median of every phase scores of the 5 items of PTS were 0 to 1. Scores of the 5 items were decreased gradually in accordance with time factor ( P=0.000) . The scores of peculiar feeling at the surgical site and discomfort in neck were different statistically during 1 m and 3 m postoperatively ( P=0.000) . Incidence of peculiar feeling at the surgical site in 1 m and 3 m postoperatively in ETAA group (54, 38.8% and 8, 5.8%) was higher than that in OT group (153, 21.2% and 20, 2.8%) . However, incidence of discomfort in neck in ETAA group (14, 10.1% and 0) was lower than in OT group (194, 26.9% and 53, 7.4%) . The other 3 items at all phases were not different statistically ( P>0.05) . The SF-36 V2 scores at 1 y postoperatively of 2 groups were not different statistically ( P=0.458) . Conclusions:PTS is a common symptom after OT or ETAA. It is frequent within early phase after thyroidectomy and is decreased significantly within 6 m. Peculiar feeling at the surgical site occurs less in OT than in ETAA in early postoperative phase and discomfort in neck occurs more, conversely.

10.
Article in Chinese | WPRIM | ID: wpr-828316

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of three pedigrees with a gestational history of fetal renal anomalies.@*METHODS@#Peripheral venous blood or skin samples were derived from the probands of the three pedigrees. Copy number variation sequencing (CNV-seq) was applied to detect alterations of genome CNVs.@*RESULTS@#The patient from pedigree 1 and the fetuses from pedigrees 2 and 3 all carried a heterozygous 17q12 deletion, with the size ranging from 1.4 Mb to 1.48 Mb encompassing the HNF1B gene.@*CONCLUSION@#The diagnosis of 17q12 microdeletion may be difficult during fetal period for its variable phenotypes. Alterations of chromosomal copy numbers need to be excluded in such patients.


Subject(s)
Humans , Chromosome Deletion , Chromosomes, Human, Pair 17 , Genetics , DNA Copy Number Variations , Fetus , Genetic Testing , Hepatocyte Nuclear Factor 1-beta , Genetics , Pedigree , Phenotype
11.
International Journal of Surgery ; (12): 658-661, 2020.
Article in Chinese | WPRIM | ID: wpr-863398

ABSTRACT

Objective:To summarize the experience of laparoscopic transabdominal preperitoneal hernia repair (TAPP) and to discuss its safety and feasibility.Methods:Data of 26 consecutive cases from January 2015 to March 2018 in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were analyzed retrospectively. They were all males, aged (68.3±14.1) years, with a range from 57 to 86 years. Body mass index was (23.3±4.1) kg/m 2. Bathel indexwas 91.4±5.6. Intraoperative main procedures were done in accordance to Guideline of Standardized Operation for Laparoscopic Inguinal Hernia Repair. A drainage tube or catheter was not routinely placed intraoperatively. Patients were discharged but for any complaints. Observation data included intraoperative, postoperative and following-up data. The following-up period was more than 12 months by telephone or clinic. The long-term complications and the changes of Barthel index were observed. Paired sample t test was used to compare the changes of Barthel index before and after operation. Results:Of the 26 cases, none was converted to open procedure and no intra- or post-operative serious complications occurred. Occurrence of surgical site seroma was 17 (65.4%) cases. The operating time was (76.5±23.6) min. Intraoperative blood loss was (8.6±4.4) mL. The postoperative hospitalization was (2.3±1.2) d. Bathel index in 1 month postoperative was 96.9±3.2. It was higher statistically than that preoperative ( t=-6.968, P=0.000). Conclusions:TAPP in the treatment of huge inguinoscrotal hernia is safe and feasible. Mastering the anatomical characteristics and the according procedures is an important factor for successful operation.

12.
Chinese Journal of Radiology ; (12): 934-940, 2020.
Article in Chinese | WPRIM | ID: wpr-868367

ABSTRACT

Objective:To explore the prognostic value of quantitative plaque analysis and coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) in evaluating plaque progression (PP).Methods:A total of 118 consecutive patients who underwent serial CCTA examinations in Affiliated Hospital of Jiangnan University from December 2013 to December 2017 were retrospectively enrolled. There were 37 patients in the PP group and 81 patients in the non-PP group. All patients′ CCTA images were quantitatively analyzed using plaque analysis software. The quantitative analysis parameters included stenosis degree, plaque length, total plaque volume, calcified plaque volume, non-calcified plaque volume, minimum lumen area, remodeling index(RI) and plaque burden. Plaque progression was defined as plaque burden change rate>1%. CT-FFR analysis was performed using cFFR software and the CT-FFR value was measured at 2-4 cm distal to the coronary lesion. Baseline parameters between the two groups were evaluated using Students t-test, U-test, chi-square test. The logistic regression model was conducted to evaluate the relationship between CCTA derived parameters and PP. Receiver operating characteristic curve analysis with the areas under the curve (AUC) was used to determine the predictive performance of different CCTA parameters. Results:Compared with the non-PP group, the patients were older( t=2.391, P=0.018), the prevalence of hyperlipidemia was higher(χ2=4.550, P=0.033), and the proportion of statins use was lower (χ2=4.764, P=0.029) in the PP group. The PP group showed greater coronary stenosis, smaller minimum lumen area, larger plaque volume and non-calcified plaque volume, larger remodeling index and lower CT-FFR value on baseline CCTA (all P<0.05). Logistic regression analysis demonstrated that RI(OR=2.714, 95%CI:1.078-6.836)and CT-FFR (OR=2.940, 95%CI:1.215-7.116) were independent predictors of PP. The model based on CCTA stenosis degree, quantitative plaque features and CT-FFR (AUC 0.83, 95%CI: 0.75-0.90; P<0.001) was significantly better than the model based on CCTA stenosis degree (AUC 0.62, 95%CI: 0.52-0.70, P=0.049) and the model based on CCTA stenosis degree and quantitative plaque characteristics (AUC 0.77, 95%CI: 0.68-0.84, P<0.001). Conclusions:Compared with the prediction model derived on stenosis degree, plaque quantitative markers and CT-FFR can improve the prediction value of PP.RI and CT-FFR were important predictors of PP.

13.
Article in Chinese | WPRIM | ID: wpr-871043

ABSTRACT

Objective:To analyze the variations of SGCA gene in two Chinese pedigrees of Han nationality with limb-girdle muscular dystrophy type 2D (LGMD2D) and provide prenatal diagnosis and genetic counseling for subsequent pregnancies within the pedigrees. Methods:This study involved two unrelated patients who were the probands of their pedigrees diagnosed with LGMD2D in the First Affiliated Hospital of Zhengzhou University from June 2017 to January 2018. Genomic DNA was extracted from peripheral blood samples of the probands and their parents. Coding sequences and flanking sequences of 21 LGMD-related genes from the probands were captured and subjected to high-throughput sequencing. Suspected mutations in their parents were detected and validated by Sanger sequencing and/or fluorescence quantitative polymerase chain reaction (PCR). Prenatal genetic diagnosis for high-risk fetuses in the two pedigrees was performed after the causative factors being identified.Results:(1) The proband of pedigree 1 carried compound heterozygous point mutations in SGCA gene with c.218C>G(p.P73R) and c.101G>A(p.R34H) inherited from his father and mother, respectively. Prenatal diagnosis indicated that the second fetus of the family carried the same mutations as the proband, and the family chose to terminate the gestation. (2) The proband of pedigree 2 inherited the compound heterozygous mutations of c.218C>T (p.P73L) and heterozygous deletion of exons 7 and 8 in SGCA gene from his parents. Their second fetus did not carry any of the above mutations and was delivered at full term. Serum creatinase level and physical, motor and mental development of the child were all within the normal range during a two-year follow-up after birth. Conclusions:The heterozygous mutations in SGCA gene are the cause of LGMD2D in the two pedigrees, and c.218C>G(p.P73R) and c.218C>T(p.P73L) are novel mutations. Genetic and prenatal diagnosis based on high-throughput targeted next-generation sequencing can rapidly and accurately detect the mutations responsible for LGMD2D.

14.
Article in Chinese | WPRIM | ID: wpr-826533

ABSTRACT

OBJECTIVE@#To carry out genetic analysis for a family with a fetus manifesting bilateral polycystic renal dysplasia and oligohydramnios at 16 gestational week and a previous history for fetal renal anomaly.@*METHODS@#Ultrasound scan was carried out to detect the morphological changes. Following genetic counselling, the parents had decided to terminate the pregnancy. Fetal kidneys were subjected to histological examination. Target capture and next generation sequencing (NGS) was applied to the abortus to detect potential variants. The results were verified by Sanger sequencing.@*RESULTS@#Histological examination of fetal kidneys revealed cystic changes without cortex, medulla or normal renal structure. NGS has identified a heterozygous c.100+1G>A variant and deletion of exon 3 of the INVS gene, which were respectively inherited from the mother and father.@*CONCLUSION@#Through NGS and Sanger sequencing, the fetus was diagnosed with type II nephronophthisis (NPHP2). Above result can provide guidance for further pregnancy and enforce understanding of clinical features and genetic etiologies for NPHP.


Subject(s)
Female , Humans , Pregnancy , Fetus , Genetic Testing , Heterozygote , Mutation , Polycystic Kidney, Autosomal Dominant , Diagnostic Imaging , Genetics , Sequence Deletion , Genetics , Transcription Factors , Genetics , Ultrasonography
15.
Article in Chinese | WPRIM | ID: wpr-826545

ABSTRACT

OBJECTIVE@#To identify pathogenic variants in two families with patients suspected for Joubert syndrome(UBST) by cerebellar vermis hypoplasia.@*METHODS@#Clinical data and peripheral venous blood and skin tissue samples were collected for the extraction of genomic DNA. Potential variants were screened by using targeted capture and next generation sequencing. Suspected variants were validated by PCR and Sanger sequencing. The frequency of the variants in the population was calculated. Pathogenicity of the variants was predicted by following the guidelines of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided to these families upon subsequent pregnancy.@*RESULTS@#The proband of family 1 was found to harbor homozygous c.2072delT (p.F691S*fs19) frameshift variant of the AHI1 gene, which may cause premature termination of translation of the Abelson helper integration site 1 after the 691st amino acid. The proband of family 2 was found to harbor compound heterozygous variants of the CPLANE1 gene, namely c.7243dupA (p.T2415Nfs*7) and c.8001delG (p.K2667Nfs*31), which can respectively lead to premature termination of translation of ciliogenesis and planar polarity effector 1 after the 2145th and 2667th amino acids. All of the three variants were previously unreported, and were predicted to be pathogenic by bioinformatic analysis.@*CONCLUSION@#The AHI1 c.2072delT and CPLANE1 c.7243dupA and c.8001delG variants probably underlay JBTS3 in family 1 and JBTS17 in family 2, respectively. Based on above results, prenatal diagnosis may be offered to the affected families upon their subsequent pregnancies.


Subject(s)
Female , Humans , Pregnancy , Abnormalities, Multiple , Diagnosis , Genetics , Adaptor Proteins, Vesicular Transport , Genetics , Cerebellum , Congenital Abnormalities , Eye Abnormalities , Diagnosis , Genetics , Genetic Testing , Genetic Variation , Kidney Diseases, Cystic , Diagnosis , Genetics , Membrane Proteins , Genetics , Mutation , Prenatal Diagnosis , Retina , Congenital Abnormalities
16.
Article in Chinese | WPRIM | ID: wpr-775761

ABSTRACT

OBJECTIVE@#To identify the pathogenic mutation underlying retinitis pigmentosa in a large pedigree.@*METHODS@#The pedigree has included three generations showing an autosomal dominant transmission of retinitis pigmentosa. Potential mutations were screened using a retinitis pigmentosa gene panel and an Ion PGM platform. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#A novel heterozygous missense mutation, c.251T>C(p.Leu84Pro), was identified in the RHO gene. The mutation has co-segregated with the retinitis pigmentosa phenotype among all family members and was not found in public databases ExAC, 1000G and dbSNP or 831 healthy controls. The mutation was predicted to be damaging by three major protein-predicting software.@*CONCLUSION@#The c.251T>C (p.Leu84Pro) mutation of the RHO gene is a novel pathogenic mutation underlying the retinitis pigmentosa phenotype in this pedigree. Above findings have enabled prenatal diagnosis for the pedigree.


Subject(s)
Humans , DNA Mutational Analysis , Eye Proteins , Mutation , Mutation, Missense , Pedigree , Phenotype , Retinitis Pigmentosa , Genetics
17.
Article in Chinese | WPRIM | ID: wpr-775791

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic diagnosis of two cases with rare diseases and X chromosome abnormalities.@*METHODS@#Multiple ligation-dependent probe amplification (MLPA) and karyotype analysis were carried out on an 8-year-old girl who was diagnosed with Duchenne muscular dystrophy. Karyotype analysis and PCR assay for SRY and AZF genes were carried out for a-2-month-old male infant with short penis.@*RESULTS@#The girl, who featured short stature and cubitus valgus, was diagnosed as Turner syndrome with a karyotype of 46,X,i(Xq). The male infant was detected with a karyotype of 45,X, with presence of SRY gene but absence of AZF gene.@*CONCLUSION@#Both cases may be associated with abnormalities of X chromosome. Genetic testing can facilitate early diagnosis and clinical intervention for such patients.


Subject(s)
Humans , Infant , Male , Chromosomes, Human, X , Karyotyping , Muscular Dystrophy, Duchenne , Genetics , Rare Diseases , Turner Syndrome , Genetics
18.
Article in Chinese | WPRIM | ID: wpr-775803

ABSTRACT

OBJECTIVE@#Genetic screening and prenatal diagnosis was performed in eighteen families with high risk of 21-hydroxylase deficiency (21-OHD) to provide valuable information for genetic counseling in these affected families.@*METHODS@#First, multiplex ligation-dependent probe amplification (MLPA) combined with nested-PCR based Sanger sequencing was used to detect CYP21A2 gene mutations in probands and their parents of eighteen families, with seven probands had been dead. Second, paternity test was applied to exclude the possibility of maternal genomic DNA contamination, and fetal prenatal diagnosis is based on the mutations found in proband or parents of the family.@*RESULTS@#Ten mutations were identified in these eighteen families, including large fragment deletion, I2G, E3del8bp, I172N, V281L, E6 cluster, L307Ffs, Q318X, R356W and R484Pfs. All probands were caused by homozygous or compound heterozygous mutations of CYP21A2 gene and their parents were carriers. By comparing short tandem repeat sites contamination of maternal genomic DNA was not found in fetal DNA. Prenatal diagnosis showed that five fetus were 21-OHD patients, four fetus were carriers and the other nine fetus were normal.@*CONCLUSION@#CYP21A2 gene mutation is the etiology of 21-OHD. Genetic testing of CYP21A2 could assist physicians in 21-OHD diagnosis and provided genetic counseling and prenatal diagnosis for parents who are at risk for having a child with congenital adrenal hyperplasia.


Subject(s)
Female , Humans , Pregnancy , Adrenal Hyperplasia, Congenital , Diagnosis , Genetics , Genetic Testing , Mutation , Prenatal Diagnosis , Steroid 21-Hydroxylase
19.
Article in Chinese | WPRIM | ID: wpr-776750

ABSTRACT

OBJECTIVE@#To carry out genetic testing for a family with two pregnancies affected with hydrops fetalis and dilated cardiomyopathy (DCM) of the fetus.@*METHODS@#DNA was extracted from fetal tissue as well as peripheral blood samples from the couple. Single nucleotide polymorphism array (SNP array) and next-generation sequencing (NGS) were carried out to screen potential mutation. Suspected mutation was validated with PCR and Sanger sequencing.@*RESULTS@#The manifestation of fetal echocardiography was consistent with DCM. No obvious abnormality was found by SNP array analysis. A hemizygous c.481G>A (p.G161R) mutation of the TAZ gene was detected in the male fetus by NGS and confirmed by Sanger sequencing. The mutation was inherited from his mother.@*CONCLUSION@#Barth syndrome due to the c.481G>A mutation of the TAZ gene probably underlies the recurrent hydrops fetalis and fetal DCM in this family.


Subject(s)
Female , Humans , Male , Pregnancy , Barth Syndrome , Genetics , Cardiomyopathy, Dilated , Genetics , Echocardiography , Genetic Testing , High-Throughput Nucleotide Sequencing , Hydrops Fetalis , Genetics , Mutation , Transcription Factors , Genetics
20.
Article in Chinese | WPRIM | ID: wpr-776805

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a pedigree affected with progressive familial intrahepatic cholestasis (PFIC).@*METHODS@#Target sequence capture and next generation sequencing (NGS) were applied for the proband. PCR and Sanger sequencing were used to verify the suspected mutation in his sister with similar symptoms and his parents.@*RESULTS@#The proband and his sister manifested after birth with symptoms including jaundice, pruritus and developmental retardation. NGS has identified compound heterozygous mutations of ABCB11 gene, which encodes bile salt export pump protein (BSEP), namely c.2494C>T (p.Arg832Cys) and c.3223C>T (p.Gln1075*), in the proband, which were inherited from his father and mother respectively. His sister carried the same compound mutations.@*CONCLUSION@#Based on the phenotype and genetic testing, the patients were diagnosed as PFIC2 caused by mutation of the ABCB11 gene. The c.3223C>T is a novel nonsense mutation which may cause premature termination of translation. Above results have enriched the spectrum of ABCB11 mutations and provided new evidence for the molecular basis of PFIC, which also facilitated genetic counseling for this pedigree.


Subject(s)
Female , Humans , Male , ATP Binding Cassette Transporter, Subfamily B, Member 11 , Genetics , ATP-Binding Cassette Transporters , Cholestasis, Intrahepatic , Genetics , Genetic Testing , Mutation , Pedigree , Phenotype
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