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1.
Article in English | WPRIM | ID: wpr-880642

ABSTRACT

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.


Subject(s)
Activities of Daily Living , Alzheimer Disease/genetics , Humans , Mutation , Neurodegenerative Diseases , Presenilin-1/genetics , Presenilin-2/genetics
2.
Chinese Journal of Lung Cancer ; (12): 338-344, 2021.
Article in Chinese | WPRIM | ID: wpr-880278

ABSTRACT

BACKGROUND@#Immune checkpoint inhibitor monotherapy is reported to have little effect in advanced non-small cell lung cancer (NSCLC) patients with driver oncogenes. However, recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy after tyrosine kinase inhibitors (TKIs) drug resistance. The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor (EGFR) sensitive mutation, and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation.@*METHODS@#A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital, Capital Medical University from June 2018 to November 2020 were collected. After the progress of targeted therapy, they had received programmed cell death protein 1 (PD-1) checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy.@*RESULTS@#Of the 27 advanced NSCLC patients, 19 cases (70.4%) did not have T790M mutation. There were 8 cases (29.6%) with T790M point mutation. The total objective response rate (ORR) was 40.7%. Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations (χ²=4.15, P=0.230). But progression-free survival (PFS) was significantly longer in patients without T790M mutation than in patients with T790M mutation (9.2 mon vs 3.3 mon, χ²=2.808, P=0.041), and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor (12.2 mon vs 7.3 mon, χ²=3.22, P=0.062). ORR of patients without T790M was significantly better than that with T790M (52.63% vs 12.5%, P=0.045).@*CONCLUSIONS@#Patients with EGFR mutation can benefit from later-line combined immunotherapy. The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line. Therefore, the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.

3.
Article in Chinese | WPRIM | ID: wpr-912418

ABSTRACT

Objective:To determine the pathogenic gene mutation in a family with incomplete congenital quiescent night blindness (CSNB) of Schubert-Bornschein type.Methods:A retrospective clinical study. In February 2021, one patient and his parents and elder brother from a Han Chinese incomplete CSNB of Schubert-Bornschein type family diagnosed by clinical and genetic examination at Henan Provincial People's Hospital were included in the study. The patient’s medical history, family history were inquired; best corrected visual acuity (BCVA), color vision, fundus color photography, full-field electroretinogram (ERG), and frequency domain optical coherence tomography (OCT) were examined in detail. Five ml of the subject’s peripheral venous blood was collected and the whole genome DNA was extracted. The genomic DNA of the subject was library constructed, and all-exon probes were polymerized for capture. The suspected pathogenic mutation site was verified by Sanger, and the pathogenicity of the gene mutation site was determined by parallel bioinformatics analysis.Results:The BCVA of both eyes of the proband (Ⅱ2) was 0.4; the color vision test could not recognize the red color. Fundus examination showed no obvious abnormalities. The retina thickness in the macular area of both eyes was slightly thinned. ERG examination of the whole field showed that the amplitude of ERG b wave was significantly reduced under the stimulation of binocular dark adaptation 3.0 and showed a negative waveform. The mother of the proband (Ⅰ2) had normal BCVA, color vision, fundus color photography, and frequency domain OCT examination. The full-field ERG examination showed that the amplitude of each eye reaction was slightly reduced, and the amplitude of the dark adaptation shock potential was significantly reduced. Genetic testing showed that the proband (Ⅱ2) had a c.1761dupC hemizygous mutation in exon 14 of the voltage-dependent calcium channel α1F subunit gene ( CACNA1F gene). The results of protein sequence homology analysis showed that the site was highly conserved in multiple species; the results of bioinformatics analysis showed that the CACNA1F gene c.1761dupC (pY588fs) subsequently had a frameshift mutation and became a stop at position 10. Codons appear translational termination in the conserved regions of the protein. According to the standards and guidelines of the American College of Medical Genetics and Genomics, the mutation was judged to be a possible pathogenic variant. The mother of the proband (Ⅰ2) was a carrier of this site mutation. The clinical and genetic test results of the father and elder brother of the proband were not abnormal. Conclusion:CACNA1F gene c.1761dupC is the pathogenic mutation site of the Schubert-Bornschein type incomplete CSNB family.

4.
Article in Chinese | WPRIM | ID: wpr-912416

ABSTRACT

Objective:To identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family.Methods:A retrospective clinical study. One child (proband) and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study. Medical history and family history, and draw pedigree of the patients was collected. Visual acuity, visual field, fundus color photography, optical coherence tomography and electroretinogram (ERG) were examined. The peripheral venous blood of the proband, his parents and sister, and extract the whole genome DNA was collected. Whole-exome sequencing was used to detect genetic variations, the suspected pathogenic variations were verified by Sanger sequencing, and the pathogenicity was determined by bioinformatics analysis.Results:The parents discovered the proband was poor vision at the age of 10 months. At the age of 3, the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4, respectively. No abnormality was found in anterior segment. Extremely high hyperopia in both eyes. The axial length was 14.47 mm and 15.78 mm, respectively. The optic disc of both eyes was relatively small and flushed, retinal folds can be observed in macular area, and no obvious pigment deposition was found. ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately, and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely. Genetic analysis revealed two novel mutations in the membrane frizzled-related protein ( MFRP) gene in the proband: c.363delC/p.Thr121Thrfs*16, c.1627C>T/p.Gln543Stop,37 in exon 4 and 13, the former was a frameshift mutation, encoding 16 amino acids and then terminated, and the latter was an nonsense mutation, truncated 37 amino acids, both which were predicted to be pathogenic and segregate with disease. The mother and sister carried c.363delC, and the father carried c.1627C>T. Conclusion:MFRP gene c.363delC/p.Thr121Thrfs*16, c.1627C >T/p.Gln543Stop, 37 compound heterozygous mutation may be the pathogenic gene of this family.

5.
Article in Chinese | WPRIM | ID: wpr-912415

ABSTRACT

Objective:To report the BEST1 gene mutations and clinical phenotypes in two pedigrees with Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). Methods:A retrospective clinical study. From November 2019 to March 2021, in the Department of Ophthalmology of The First Affiliated Hospital of Zhengzhou University, the BVMD family (4 patients and 6 family members) and the ARB family (2 patients, 2 family members), a total of 6 patients and 8 normal family members were included in the study. Detailed medical history was obtained; best corrected visual acuity, fundus color photography, electrophysiology, optical coherence tomography and fundus autofluorescence examination were performed. The clinical characteristics for all patients in the two families were analyzed. Three milliliter peripheral venous blood of all participants in the family was collected, and the whole genomic DNA was extracted with gene sequencing using next-generation sequencing technology based on targeted capture. Compared with the database to identify the pathogenicity mutation sites, suspected pathogenic mutation sites were selected, then mutations in other members in the family was assayed by Sanger sequencing.Results:In family 1, the proband was demonstrated as typical BVMD, other patients were multifocal vitelliform macular dystrophy. The DNA sequencing result showed that all the 4 patients carried heterozygous missense mutations in exon 3 of BEST1 gene: c.240C>G (p.F80L) (M1) and 2 members carried this mutation, but without clinical phenotype. M1 was a likely-pathogenic mutation reported for the first time. In family 2, the proband and the other patient were diagnosed as ARB. The DNA result showed that the 2 patients carried heterozygous missense mutations in exon 5 and exon 2 of BEST1 gene: c.584C>T (p.A195V) (M2)、c.139C>A (p.R47S) (M3), and a heterozygous frameshift mutation in exon 3 of BEST1 gene: c.235dupT (p.S79Ffs*153) (M4). M2 was a pathogenic mutation reported previously. M3 variant was of undetermined significance. M4 was a first reported pathogenic mutation. Conclusions:The BEST1 gene mutation is the main cause of BVMD and ARB. Different mutation sites have different clinical phenotypes. BVMD and ARB have genetic and clinical heterogeneity.

6.
Chinese Journal of Neurology ; (12): 1299-1302, 2021.
Article in Chinese | WPRIM | ID: wpr-911870

ABSTRACT

Nonketotic hyperglycinemia (NKH) is a rare congenital metabolic disorder with low diagnostic rate. This article reported a case of NKH caused by AMT gene mutation. The child started with suspected neonatal sepsis, and then the condition deteriorated rapidly, including apnea, hiccup, coma, convulsion, etc. Blood glucose, ketone body, blood gas analysis of electrolytes, blood ammonia and so on were generally normal. Blood and urine screening results showed that glycine was slightly higher, and the ratio of cerebrospinal fluid to serum glycine concentration increased. Electroencephalogram showed outburst suppression. High total exome sequencing results showed that the maternal exon 3 c.664C>T(p.Arg222Cys) of AMT gene was pathogenic, and the paternal exon 3 c.793C>T(p.Arg265Cys) was suspected to be pathogenic, which was an autosomal recessive genetic disease with complex heterozygosis. The clinical diagnosis and treatment of this child and the characteristics of gene mutation are summarized.

7.
Article in Chinese | WPRIM | ID: wpr-911604

ABSTRACT

Objective:To investigate the correlation between cervical lymph node metastasis,extra thyroidal extension and other clinicopathologic features and BRAF V600E gene mutation abundance in papillary thyroid carcinoma. Methods:The clinicopathologic data of 123 PTC patients admitted from Jan 2018 to Oct 2020 in Peking University People's Hospital were analyzed retrospectively. All the PTC cases were examined by next generation sequencing technology. BRAF V600E gene mutation abundances were detected and analyzed with different clinicopathologic features, and differences between groups were compared. Results:There were statistical differences compared to control group in BRAF V600E gene mutation abundances in lymph node metastasized group and extra thyroidal extended group(all P<0.05). BRAF V600E gene mutation abundances were positively related with severity of extra thyroidal extension( P<0.05). Conclusion:BRAF V600E gene mutation abundance was related with cervical lymph node metastasis and extra thyroidal extension in PTC patients.

8.
Article in Chinese | WPRIM | ID: wpr-911367

ABSTRACT

In the present study, the clinical features of a patient with autosomal recessive hypophosphatemic rickets 1 caused by dentin matrix protein 1(DMP1)gene mutation and her family members were investigated. DMP1 gene from peripheral blood was sequenced by Sanger sequencing, and the known mutation was verified among her family members and 250 healthy populations. The proband was a 42-year-old female with bone deformity of both lower limbs, bone pain, and short stature. The results of X-rays and laboratory examination were consistent with the hypophosphatemic rickets reported before. A homozygous mutation(c.2T> C)in DMP1 was identified by Sanger sequencing in the proband, her son and daughter were heterozygous for c. 2T> C.

9.
Article in Chinese | WPRIM | ID: wpr-908067

ABSTRACT

To analyze the clinical characteristics and genetic data of a child with type Ⅱ Bruce syndrome (type Ⅱ BS) admitted to the Department of Orthopedics, Shanxi Children′s Hospital at May 2020.A 3-day-old boy was admitted due to the pain and swelling of the right lower limb 3 days after birth.Due to the patient had multiple fractures, callus formation after clavicle and rib fracture, greendstick fracture of the humerus, right femur fracture, left tibia and fibula fracture, congenital clubfoot, and congenital contracture of wrist, elbow, hip and knee joint, and therefore, chromosome diseases were considered.Gene sequencing data showed gene mutation in PLOD2 with compound heterozygosity deletion of the child (proband), and mutation and heterozygosity deletion came from their parents, respectively.The patient was diagnosed as type Ⅱ BS.This case report alarms clinicians to identify a missense mutation of PLOD2 and loss of heterozygosity, so as to reduce the misdiagnosis rate and achieve early diagnosis and treatment.

10.
Article in Chinese | WPRIM | ID: wpr-908034

ABSTRACT

Objective:To explore the clinical characteristics of Diamond-Blackfan anemia (DBA) in children caused by RPL5 gene mutation, thus improving the understanding of the etiology of DBA.Methods:The clinical data and sequencing results of a child with DBA caused by RPL5 gene mutation treated in the Children′s Hospital of Fudan University were analyzed.In addition, through literature review of reported DBA cases at domestic and home, summarized the clinical features of DBA.Results:The patient was an 8-year-old male child.Bone marrow puncture examination of the child showed DBA, and a heterozygous mutation of RPL5 gene c. 657C>G, p.Y219X was identified for the first time in the DBA case.A total of 47 cases of DBA were retrieved from the online databases plus the one reported in this study (48 cases in total), and their clinical features were summarized as follows: the incidence of DBA was similar in men and women.The number of DBA patients in Asia was lower than that in Europe and the United States.DBA was mainly a sporadic disease.Among the exon mutations in European and American cases of DBA, 43.0% of them had mutations in Exon3.The malformation rate of DBA patients with RPL5 mutation was 81.3% (39/48 cases, excluding short stature cases), which was higher than that of patients with other mutation types.The response rate of glucocorticoid therapy for DBA was 46.0%, which was lower than that of the overall response rate.Conclusions:chr1: 93303142(c.657 C>G, p.Y219X) is a newly detected mutation of RPL5 gene in the DBA case, which expands the pathogenic gene spectrum of DBA.Patients with RPL5 mutation have higher rates of teratogenicity and multiple teratogenicity, and a lower response rate to hormone therapy.

11.
Article in Chinese | WPRIM | ID: wpr-907847

ABSTRACT

BRAF V600E mutation is a common gene mutation in papillary thyroid carcinoma (PTC) , which is associated with the occurrence, development, and prognosis of PTC. TERT promoter mutations are rare in PTC, but PTC with its mutations is more aggressive and has a worse prognosis. Clinically, a small number of PTC patients have both BRAF V600E mutation and TERT promoter mutations. This article provides a brief overview of the co-mutation of BRAF V600E and TERT promoter and the occurrence and development, clinical diagnosis, surgical strategies, postoperative adjuvant treatment, and prognosis of PTC.

12.
Article in Chinese | WPRIM | ID: wpr-907282

ABSTRACT

Infantile liver failure syndrome-2(ILFS2)is a rare autosomal recessive disorder caused by neuroblastoma amplified sequence(NBAS)gene mutation, manifested as recurrent acute liver failure(ALF)with fever/infection-related pathogenesis.First-onset ALF is common in infants or early childhood(8 months to 3 years of age). The main characteristic of this disease is that the liver function can be recovered completely in the interval, and the definitive diagnosis is based on the identification of NBAS gene mutation in gene analysis.Until now, the pathogenesis of ILFS2 is not yet fully understood.Patients can be treated by supportive treatment clinically, while liver transplantation is the only treatment option currently available for patients with end-stage ALF.This review will focus on the recent progress in the pathogenesis and treatment of ILFS2.

13.
International Eye Science ; (12): 1191-1195, 2021.
Article in Chinese | WPRIM | ID: wpr-877381

ABSTRACT

@#Congenital cataract is one of the leading causes of childhood blindness and congenital membranous cataract is a rare and special type of congenital cataract. The lens fibre of congenital membranous cataract is degenerative and its cortex is absorbed gradually. Congenital membranous cataract also has another name, pseudoaphakia, due to the similar phenotype with posterior capsule opacification after cataract surgery, but without intraocular refractive power. There are few reports on congenital membranous cataract at home and abroad, and the research on the pathogenesis of congenital membranous cataract is even less. Clarifying the pathogenesis of congenital membranous cataract, especially the genetics, is very helpful for us to understand the pathogenesis of congenital cataract and the molecular mechanism of lens development.

14.
Organ Transplantation ; (6): 588-2021.
Article in Chinese | WPRIM | ID: wpr-886788

ABSTRACT

Objective To evaluate the clinical efficacy of heterozygous living donor liver transplantation for pediatric maple syrup urine disease. Methods A 3-year-old boy was admitted to the hospital on July 5, 2017 due to maple syrup urine disease for half a year. The child presented with paroxysmal dysarthria and motor dysfunction of the lower limbs under fasting status for half a year, accompanied with obvious maple syrup urine odor and slow language development. No other growth abnormality or mental defects were observed. Serum branched chain amino acid (BCAA) assay detected that the level of leucine was 684 μmol/L and 559 μmol/L for the valine. The child was diagnosed with maple syrup urine disease type b based on gene detection combined with BCAA assay. Living donor liver transplantation from his biological father was performed. Postoperatively, routine immunosuppression, anti-virus, anti-infection therapies, maintenance of fluid, electrolyte, and acid-base balance and other necessary nutritional support were given. The dose of tacrolimus was adjusted according to biochemical parameters and cytochrome P450(CYP)3A5 genotype of the recipient. Glucocorticoid administration was terminated at approximately 6 months after operation. Results The liver function of the recipient was recovered to normal range at postoperative 1 month, and basically stabilized at 3 years after surgery. The amino acid level was decreased to normal level immediately after operation, and BCAA was continually declined after normal diet for postoperative 1 month. As of the submission date, the recipient grew well in a stable condition and achieved high quality of life. Conclusions Heterozygous living donor liver transplantation is a safe and effective treatment of maple syrup urine disease, which reduces the possibility of sudden acute metabolic events, significantly improves the quality of life of the recipient and provides a novel idea for surgical treatment of maple syrup urine disease.

15.
Article in Chinese | WPRIM | ID: wpr-882186

ABSTRACT

@#Hemangiomas and vascular malformations are common clinical diseases. According to their clinical and imaging characterizations, the International Society for the Study of Vascular Anomalies (ISSVA) has systematically classified infantile hemangioma and vascular malformations, and the classification has been widely recognized and applied. To date, most vascular malformations involve the following important signaling pathways: PI3K/Akt/mTOR and RAS/MAPK/ERK. This discovery has major impacts on the diagnosis and treatment of vascular malformations including the following: the understanding of the biology of vascular malformations has been increased; the understanding of vascular malformations based on genotype has been refined; and the development of targeted drugs for the treatment of vascular malformations has been promoted. Despite facing many challenges, with the development of gene sequencing, molecular biology and imaging technology, the relevance of vascular malformation classification and the accuracy of diagnosis are improving, and this is accompanied by innovations in surgical treatment and sclerotherapy, interventional embolization, and continuous progress in targeted therapy. At present, investigations on vascular malformations are mostly retrospective clinical studies or low-level clinical trials. The purpose of this paper is to review the literature on the treatment of infantile hemangioma, lymphatic malformation, venous malformation and arteriovenous malformation and to review the research progress in evidence-based treatment of infantile hemangioma and vascular malformation.

16.
Organ Transplantation ; (6): 77-2021.
Article in Chinese | WPRIM | ID: wpr-862779

ABSTRACT

Objective To investigate the clinical characteristics and the experience of multi-disciplinary team (MDT) on recurrence of primary hyperoxaluria (PH) type I after renal transplantation. Methods One case presenting with unexplained rapid decline of renal allograft function after allogeneic renal transplantation was discussed by MDT. The role of MDT in diagnosing rare hereditary diseases and improving the long-term survival of renal transplant recipients was summarized. Results After MDT consultation, the patient was diagnosed with recurrence of PH type I. Routine immunosuppressive regimen was initiated after the exclusion of rejection. The patient was instructed to drink a large quantity of water, and given with high-quality protein and low-phosphorus diet, vitamin B6, calcium and other conservative therapies to actively prevent and treat postoperative complications. The deterioration of renal graft function was delayed. Nevertheless, regular hemodialysis was resumed at 5 months after renal transplantation until the submission date of this manuscript. Conclusions Recurrence of PH type I after renal transplantation is relatively rare. The main clinical manifestations are recurrent kidney stones and decreased renal function with multiple complications and poor prognosis. The condition of the patient is consulted by MDT for confirming the diagnosis, determining the optimal treatment scheme, delaying the progression and improving the clinical prognosis.

17.
Article in Chinese | WPRIM | ID: wpr-861653

ABSTRACT

Objective: To analyze the clinicopathological features of small cell lung cancer transformed from lung adenocarcinoma. Methods: We retrospectively analyzed the clinical and pathological characteristics and follow-up data of seven patients who had been diagnosed with small cell lung cancer transformed from lung adenocarcinoma following treatment from January 2014 to December 2018 at the Fourth Hospital of Hebei Medical University. Results: The latest follow-up had been performed on June 1, 2020. The median time of small cell lung cancer transformation from lung adenocarcinoma following treatment was 31 months; the median time of tyrosine kinase inhibitor (TKI) application before transformation is 14 months. Three patients had transformation at the same site as the original. Seven patients had higher levels of neuron-specific enolase (NSE) before transformation. Before the transformation, disease progression mostly occurred at multiple sites, and the lung, bone, brain, pleura, and lymph nodes were commonly affected. In all cases, immunohistochemical indicators after transformation showed that thyriod transcription factor-1 (TTF-1) was positive; Napsin A was negative; Syn, CD56, and AE1/AE3 were positive; Ki67 expression was high; and PD-L1 expression was negative. Genetic testing after transformation showed that six patients had maintained the original mutant EGFR gene. Treatments after transformation were mainly comprehensive, based on chemotherapy. The median progression-free survival time after transformation was 6 months, and median survival time after transformation for five patients who died was 10 months. Conclusions: Once lung adenocarcinoma undergoes transformation to small cell lung cancer, the disease progresses rapidly, and survival time is short. Patients with lung adenocarcinoma due to EGFR E19 mutation who undergo EGFR-TKI therapy are more prone to small cell lung cancer transformation, and the time to transformation generally exceeds 2 years. The sites of disease progression before transformation are often multiple, and NSE is increased. After transformation, patients generally maintain the original EGFR mutation.

18.
Article in English | WPRIM | ID: wpr-879952

ABSTRACT

The pathogenesis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site,resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S,C,and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes,leading to the HCC occurrence. In this article,the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed,so as to provide insights into the prevention,early prediction and postoperative adjuvant therapy of HCC.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B/complications , Hepatitis B virus/genetics , Hepatocytes , Humans , Liver Neoplasms
19.
Article in Chinese | WPRIM | ID: wpr-879266

ABSTRACT

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.


Subject(s)
Animals , Carcinoma, Papillary/genetics , Humans , Lymphatic Metastasis , Mice , Mutation , Oncogenes , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics
20.
Article in Chinese | WPRIM | ID: wpr-878693

ABSTRACT

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.


Subject(s)
Cervical Vertebrae , Child , Cohort Studies , Female , Glycoproteins , Humans , Klippel-Feil Syndrome/genetics , Male , Mutation , Nuclear Proteins , Radiography , Transcription Factors/genetics
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