ABSTRACT
A total of 4 patients with renal cancer were admitted to our hospital from October 2006 to September 2015 in a familial renal cancer family. Among the 4 patients, 1 patient showed unilateral multiple clear cell carcinoma, 1 patient showed bilateral multiple clear cell carcinoma, and 2 patients showed bilateral multiple chromophobe cell carcinoma. No mutation of VHL or FLCN gene was found in all patients by genetic analysis.
ABSTRACT
Objective:To analyze the clinical characteristics and transthyretin ( TTR) gene mutation of a family with familial vitreous amyloidosis (FVA). Methods:A pedigree investigation was performed.The clinical data of 20 family members of a Han family with FVA treated in the Affiliated Hospital of Guizhou Medical University from May 2005 to March 2019 were collected, including demographic data and ophthalmic examination results.Nine eyes of five patients underwent vitrectomy successively, and vitreous samples collected during operation were sent for pathological examination by Congo red staining.The best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured, and the anterior segment as well as fundus was observed under the slit lamp microscope at 1 week and 6 months after surgery.Peripheral venous blood (4 ml) was collected from 20 members in this family and DNA was extracted.The next-generation sequencing technology was used for gene detection of proband, and Sanger sequencing was performed in 20 family members including the proband.The pathogenicity of the mutation sites was analyzed according to ACMG guidelines.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Affiliated Hospital of Guizhou Medical University (No.2019-296). Written informed consent was obtained from each subject.Results:The preoperative BCVA of the nine eyes (5 patients) remained 0.1 to 0.2 in 6 eyes, and counting fingers to 50 cm in 3 eyes, and the mean value of preoperative IOP was (15.18±1.32) mmHg (1 mmHg=0.133 kPa). Cotton-wool like opacity in the vitreous and white pedal disc punctate granule on the posterior lens capsule were seen in the 9 eyes under the slit lamp microscope.Vitreous specimens of patients were Congo red stain positive.The BCVA remained 0.8 in 8 eyes and 0.6 in 1 eye at 1 week after vitrectomy, and remained 0.8 in 6 eyes, 0.6 in 2 eyes and light perception in 1 eye at 6 months after surgery.Mean values of postoperative IOP were (15.32±2.11) mmHg and (16.13±1.25) mmHg at 1 week and 6 months after surgery, respectively.Secondary glaucoma occurred in 8 eyes at 3 to 14 years postoperatively.Mean BCVA of the 13 phenotypic normal family members (26 eyes) remained 0.8 to 1.0, and the mean value of IOP was (15.52±1.15) mmHg, and abnormalities were not found in anterior segment or fundus.Additionally, two members (4 eyes) failed to take examinations.Genetic testing revealed heterozygous mutation in p. Gly103Arg of TTR gene in 15 family members.According to ACMG guidelines, the variation score was PS1+ PM2+ PP3, and it was likely pathogenic. Conclusions:The secondary glaucoma is of relatively high incidence in patients with FVA after vitrectomy.The heterozygous mutation of TTR gene (p.Gly103Arg) might be the variation site of the family with vitreous amyloidosis.
ABSTRACT
Objective:To investigate the clinical characteristics of two Han families with familial vitreous amyloidosis (FVA) and the gene mutation.Methods:A pedigree investigation was performed.Two Han Chinese families with FVA treated in Xiangya Hospital of Central South University from January 2015 to December 2018 were collected.General examination and ophthalmic examination were performed among 112 members of the two families.Peripheral blood samples were collected from 32 family members (15 patients in MZ001 pedigree, 7 patients in MZ002 pedigree, and 5 persons with normal clinical phenotype from each pedigree) for DNA extraction, polymerase chain reaction (PCR) amplification, transthyretin ( TTR) gene screening and sequencing.Vitreous biopsy following three-channel 23-gauge pars plana vitrectomy was performed on the two probands in the two families.Vitreous specimens were sent for pathological examination.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Xiangya Hospital of Central South University (No.201412463), and written informed consent was obtained from all subjects before any medical examination. Results:In MZ001, there were 15 cases of the 63 members presented bilateral vitreous opacity at an average age of (43.6±5.8) years.No lesion was found in nervous system, cardiovascular system, kidney or liver in general inspection.The vitreous of the proband (Ⅲ13) was so sticky that could not be totally removed during vitrectomy.The vitreous specimen showed positive Congo red staining.Ⅲ13 had elevated intraocular pressure after vitrectomy and was diagnosed as open-angle glaucoma.Gene sequencing revealed Gly83Arg mutation in the exon 3 of TTR gene.In MZ002, 7 cases of 49 members had bilateral vitreous opacity at an average age of (50.4±5.5) years, among which, 3 cases appeared symptoms of limb numbness and decreased muscle strength.The vitreous body of the proband (Ⅱ11) in MZ002 pedigree was looser and easier to remove during vitrectomy than that of Ⅲ13 in MZ001 pedigree.Vitreous specimen of Ⅱ11 was positive with Congo red staining.Gene sequencing revealed an Ala36Pro variant in the exon 3 of TTR gene. Conclusions:Gly83Arg or Ala36Pro mutation of TTR gene can cause FVA.Different mutations can lead to different clinical phenotypes such as age of onset, clinical symptoms and complications of other systems.
ABSTRACT
Objective To analyze the birth order of gastric cancer patients in Shanxi Provincial Cancer Hospital,and to explore the relationship between environmental factors,genetic factors and gastric cancer.Methods The Greenwood and Yule,Haldane and Smith birth order methods were used to conduct an epidemiological investigation on 554 patients with gastric cancer surgery from January 2004 to December 2007 in Shanxi Provincial Cancer Hospital,and the birth order of their siblings was studied.Results Results from the Greenwood and Yule method showed that there was a tendency for patients with gastric cancer in birth order first to third.However,the Haldane and Smith method showed that the results were quite different between actual value and the average theory value of 6A [6A(actual value)=7 644,(x)6A(average theory value)=8 511,x=|6A-(x)6A|/√v6A=4.86,x＞2,P <0.01] which suggested that the birth order had some effects on the occurrence of gastric cancer.In addition,the actual value of 6A was lower than theoretic average value,and the parents at younger productive age or baby at the first birth was easy to develop gastric cancer.Conclusions Gastric cancer patients in Shanxi Provincial Cancer Hospital is related with the birth order,especially at early order.There are certain effects of environmental risk factors on gastric cancer.
ABSTRACT
Objective To investigate the methylation alteration of genomic DNA (gDNA) and its significance in pedigree neural tube defects (NTDs).Methods Twelve subjects from 3 NTDs pedigrees were enrolled in this study.NTDs patients were served as the case group,and their family members with normal phenotype were served as the control group.Peripheral vein blood was extracted,then gDNA was extracted.The extracted gDNA was treated with sodium bisulfite propagated as DNA segments in the way of whole genome amplification,which was put in I11umina Infinium human methylation 450k bead chip to perform hybridization,elution,extension,and imaging.The chip was scanned by iScan.Genome Studio was used to read the outcome.Illumina methylation analyzer software was used to analyze the methylation data.Results Gene differential methylation analysis showed that differential methylation sites only accounted for 0.2％ of the detected CpG sites and there were 617 differential hypermethylation sites (P ＜ 0.05),and 63 of them represented significant difference(P ＜ 1 × 10-4),including zinc finger E-box binding homebox 2,5,10-methylenetetrahydrofolate dehydrogenase 1 etc;there were 104 differential hypomethylation sites (P ＜ 0.05),and 65 of them represented significant difference (P ＜ 0.01),including Homeobox B7 and runt-related transcription factor 3 etc.Clustering analysis indicated that the tendency of DNA hypermethylation was consistent with NTDs patients,but the tendency of DNA hypomethylation was consistent with the controls.Conclusion In NTDs pedigree,the abnormal DNA methylation alterations may be the risk factor for NTDs occurrence.
ABSTRACT
Objective To investigate the methylation alteration of genomic DNA (gDNA) and its significance in pedigree neural tube defects (NTDs).Methods Twelve subjects from 3 NTDs pedigrees were enrolled in this study.NTDs patients were served as the case group,and their family members with normal phenotype were served as the control group.Peripheral vein blood was extracted,then gDNA was extracted.The extracted gDNA was treated with sodium bisulfite propagated as DNA segments in the way of whole genome amplification,which was put in I11umina Infinium human methylation 450k bead chip to perform hybridization,elution,extension,and imaging.The chip was scanned by iScan.Genome Studio was used to read the outcome.Illumina methylation analyzer software was used to analyze the methylation data.Results Gene differential methylation analysis showed that differential methylation sites only accounted for 0.2％ of the detected CpG sites and there were 617 differential hypermethylation sites (P ＜ 0.05),and 63 of them represented significant difference(P ＜ 1 × 10-4),including zinc finger E-box binding homebox 2,5,10-methylenetetrahydrofolate dehydrogenase 1 etc;there were 104 differential hypomethylation sites (P ＜ 0.05),and 65 of them represented significant difference (P ＜ 0.01),including Homeobox B7 and runt-related transcription factor 3 etc.Clustering analysis indicated that the tendency of DNA hypermethylation was consistent with NTDs patients,but the tendency of DNA hypomethylation was consistent with the controls.Conclusion In NTDs pedigree,the abnormal DNA methylation alterations may be the risk factor for NTDs occurrence.
ABSTRACT
Objective To explore the relationship between esophagus cancer patients and both environmental and genetic factors,through analyzing the data on birth orders from esophagus cancer patients of Shanxi province.Methods Both Greenwood and Haldane methods on birth order were used to study the 1101 cases with esophagus cancer from Shanxi province.All the patients had received surgery and were diagnosed,by pathological evidence.First certificates of the patients were confirmed through the standard genetic epidemiologic investigation.Birth order was investigated on probands of the 1101 cases with esophagus cancer and their 44 siblings.Results Results form the Greenwood method showed that there was a tendency for cases with esophagus cancer in birth orders First to Third.However,the Haldane method showed that the results were quite different between actual value and the average theory value of 6A (6A(actual value)=17 118,(X)6A(average theory value) =19 290,X=∣6A-(X)6A∣/√V6A =7.63,X ＞ 2) which suggested that the birth order had some effects on the occurrence of esophagus cancer.In addition,the actual value of 6A was lower than the theoretic average value,and the parents at younger productive age or baby at the first birth was easy to develop esophagus cancer.Conclusion Esophagus cancer was related with the birth order,especially at early order,which was not consistent with the national reports on esophagus cancer.Results from this study suggested that there were certain effects of environmental risk factors on esophagus cancer patients.
ABSTRACT
Background Stickler syndrome is a genetic connective tissue disorder that affects the ocular,skeletal,orofacial and auditory systems.To determine the gene mutation loci can offer a basis for genetic diagnosis and management of Stickler syndrome.Objective The aim of this study was to research the clinical characteristics of a pedigree with Stickler syndrome and identify the disease-causing gene mutation.Methods This study was approved by Ethic Committee of Peking Union Medical College Hospital.The clinical study and pedigree analysis were performed in one family with Stickler syndrome type Ⅰ (STL Ⅰ).Nine family members were examined with informed consent.The entire coding regions of COL2A1 gene with flanking intronic regions were amplified by PCR and directly sequenced.The detected sequence change was confirmed to be mutationloci by examining whether they existed in normal control individuals.Mutant proteins were predicted with online software.Results There were 4 generations and 11 members in this family,and 2 members died,including 1 patient.Three patients were found in 9living families.Inheritance of this family complicd with an autosomal dominant inheritance mode.All affected individuals showed the consistent phenotypes with STL Ⅰ,including high myopia,membranous vitreous anomaly and surface central flat,short nose,palatoschisis,etc.Mutation screening of COL2A1 gene revealed that the first base of intron 12 was deleted(IVS12+1G del).Nucleotide sequence analysis showed that this mutation led to the functional abnormal of this gene by forming termination cordon in advance.This mutation occurred in all affected individuals,however,no mutation was observed in any unaffected member or 100 normal unrelated individuals.Conclusions This study identifies a novel splice-site mutation(IVS12+ 1G del)in COL2A1 gene in a Chinese STL Ⅰ pedigree.This is the first report on a mutation in a Chinese STL Ⅰ family.
ABSTRACT
BACKGROUND: Malignant hyperthermia (MH) is a disorder of the skeletal muscle manifested as a life threatening hypermetabolic crisis in susceptible individuals following exposure to inhalation anesthetics and depolarizing muscle relaxants. MH susceptibility (MHS) is inherited as an autosomal dominant trait and mutations in the gene encoding skeletal muscle ryanodine receptor (RYR1) are considered a common cause of the disorder. To date, more than 25 RYR1 mutations have been reported in families from Europe and North America. In Korea, however, little is known about the mutations in this candidate gene. METHODS: For the analysis of novel or previously published known RYR1 mutations in 13 exons of the RYR1 gene, PCR amplification and direct sequencing were performed in the proband. After identification of RYR1 mutation in the proband, we performed an extended pedigree study with informed consent from 160 members of a Korean MH family. DNA from 160 members of this family was screened for the presence or absence of RYR1 mutation identified in the proband. RESULTS: We identified a heterozygous G7304A mutation (Arg2435His) in exon 45 of the RYR1 gene in the proband. Six members of the family suffered fatal MH reaction and died. Two members including this proband had a fulminant MH episodes but survived. Two members of the family had presented with severe muscle hypotonia. PCR amplification for the screening of the site yields a fragment of 256 base pair (bp), which is fully cleaved into two fragments of 169 bp and 87 bp by Hga1 in normal individuals and 50% cleaved in individuals with a heterozygous mutation. We found the heterozygous G7304A mutation in 30 individuals from the 160 family members. CONCLUSIONS: This result is the first report to identify the mutation of RYR1 in patients with malignant hyperthermia in Korea. Further larger scale studies will provide important data regarding the frequency of occurrence of the RYR1 mutations in Korea and insight into the practicality of genetic screening relative to diagnosis of MHS and prevention of MH episodes and MH-related problems.