scholarly journals Jervell and Lange-Nielsen Syndrome due to a Novel Compound Heterozygous KCNQ1 Mutation in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yue Qiu ◽  
Sen Chen ◽  
Xia Wu ◽  
Wen-Juan Zhang ◽  
Wen Xie ◽  
...  
Keyword(s):  
Deaf Child ◽  
Gene Mutations ◽  
Deaf Children ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Qtc Interval ◽  
Cardiac Events ◽  
Life Threatening ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Jervell and Lange-Nielsen syndrome (JLNS) is a rare but severe autosomal recessive disease characterized by profound congenital deafness and a prolonged QTc interval (greater than 500 milliseconds) in the ECG waveforms. The prevalence of JLNS is about 1/1000000 to 1/200000 around the world. However, exceed 25% of JLNS patients suffered sudden cardiac death with kinds of triggers containing anesthesia. Approximately 90% of JLNS cases are caused by KCNQ1 gene mutations. Here, using next-generation sequencing (NGS), we identified a compound heterozygosity for two mutations c.1741A>T (novel) and c.477+5G>A (known) in KCNQ1 gene as the possible pathogenic cause of JLNS, which suggested a high risk of cardiac events in a deaf child. The hearing of this patient improved significantly with the help of cochlear implantation (CI). But life-threatening arrhythmias occurred with a trigger of anesthesia after the end of the CI surgery. Our findings extend the KCNQ1 gene mutation spectrum and contribute to the management of deaf children diagnosed with JLNS for otolaryngologists (especially cochlear implant teams).

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

scholarly journals Novel SPG 11 Mutations in Hereditary Spastic Paraplegia With Thin Corpus Callosum in a Chinese Family

2016 ◽  
Vol 43 (6) ◽  
pp. 833-840
Author(s):  
Xiaojie Tian ◽  
Min Wang ◽  
Kaiyuan Zhang ◽  
Xinqing Zhang
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Gene Mutations ◽  
Protein Product ◽  
Exome Capture ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Spastic Paraplegia ◽  
Reading Frame ◽  
Physical Examinations ◽  
Compound Heterozygous Mutations

AbstractBackground: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease that is characterized by progressive weakness and spasticity of the lower extremities; HSP can present as complicated forms with additional neurological signs. More than 70 disease loci have been described with different modes of inheritance. Methods: In this study, nine subjects from a Chinese family that included two individuals affected by HSP were examined through detailed clinical evaluations, physical examinations, and genetic tests. Targeted exome capture technology was used to identify gene mutations. Results: Two novel compound heterozygous mutations in the SPG 11 gene were identified, c.4001_4002insATAAC and c.4057C>G. The c.4001_4002insATAAC mutation leads to a reading frame shift during transcription, resulting in premature termination of the protein product. The missense mutation c.4057C>G (p.H1353D) is located in a highly conserved domain and is predicted to be a damaging substitution. Conclusions: Based on the results described here, we propose that these novel compound heterozygous mutations in SPG 11 are the genetic cause of autosomal recessive HSP in this Chinese family.

scholarly journals Methylmalonic Acidemia with Novel MUT Gene Mutations

2017 ◽  
Vol 2017 ◽  
pp. 1-2
Author(s):  
Inusha Panigrahi ◽  
Savita Bhunwal ◽  
Harish Varma ◽  
Simranjeet Singh
Keyword(s):  
Sanger Sequencing ◽  
Gene Mutations ◽  
Methylmalonic Acidemia ◽  
Feeding Problems ◽  
Novel Variants ◽  
Mut Gene ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Poor Weight Gain

A 5-year-old boy presented with recurrent episodes of fever, feeding problems, lethargy, from the age of 11 months, and poor weight gain. He was admitted and evaluated for metabolic causes and diagnosed as having methylmalonic acidemia (MMA). He was treated with vit B12 and carnitine supplements and has been on follow-up for the last 3 years. Mutation analysis by next generation sequencing (NGS), supplemented with Sanger sequencing, revealed two novel variants in the MUT gene responsible for MMA in exon 5 and exon 3, respectively. Recently he developed dystonic movements including orofacial dyskinesia. With advent of NGS, judicious use of NGS with Sanger sequencing can help identify causative possibly pathogenic mutations.

scholarly journals The Potential Role of Aldosterone-Producing Cell Clusters in Adrenal Disease

2020 ◽  
Vol 52 (06) ◽  
pp. 427-434
Author(s):  
Jung Soo Lim ◽  
William E. Rainey
Keyword(s):  
Gene Mutations ◽  
Normal Subjects ◽  
Secondary Hypertension ◽  
Cell Clusters ◽  
Somatic Gene ◽  
Aldosterone Production ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Made In

AbstractPrimary aldosteronism (PA) is the most common cause of secondary hypertension. The hallmark of PA is adrenal production of aldosterone under suppressed renin conditions. PA subtypes include adrenal unilateral and bilateral hyperaldosteronism. Considerable progress has been made in defining the role for somatic gene mutations in aldosterone-producing adenomas (APA) as the primary cause of unilateral PA. This includes the use of next-generation sequencing (NGS) to define recurrent somatic mutations in APA that disrupt calcium signaling, increase aldosterone synthase (CYP11B2) expression, and aldosterone production. The use of CYP11B2 immunohistochemistry on adrenal glands from normal subjects, patients with unilateral and bilateral PA has allowed the identification of CYP11B2-positive cell foci, termed aldosterone-producing cell clusters (APCC). APCC lie beneath the adrenal capsule and like APA, many APCC harbor somatic gene mutations known to increase aldosterone production. These findings suggest that APCC may play a role in pathologic progression of PA. Herein, we provide an update on recent research directed at characterizing APCC and also discuss the unanswered questions related to the role of APCC in PA.

scholarly journals Identification of a Novel Heterozygous Missense Mutation in theCACNA1FGene in a Chinese Family with Retinitis Pigmentosa by Next Generation Sequencing

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Qi Zhou ◽  
Jingliang Cheng ◽  
Weichan Yang ◽  
Mousumi Tania ◽  
Hui Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Missense Mutation ◽  
Clinical Signs ◽  
Chinese Family ◽  
Next Generation ◽  
Heterozygous Missense Mutation ◽  
Peripheral Leukocytes ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Background.Retinitis pigmentosa (RP) is an inherited retinal degenerative disease, which is clinically and genetically heterogeneous, and the inheritance pattern is complex. In this study, we have intended to study the possible association of certain genes with X-linked RP (XLRP) in a Chinese family.Methods.A Chinese family with RP was recruited, and a total of seven individuals were enrolled in this genetic study. Genomic DNA was isolated from peripheral leukocytes, and used for the next generation sequencing (NGS).Results.The affected individual presented the clinical signs of XLRP. A heterozygous missense mutation (c.1555C>T, p.R519W) was identified by NGS in exon 13 of theCACNA1Fgene on X chromosome, and was confirmed by Sanger sequencing. It showed perfect cosegregation with the disease in the family. The mutation at this position in theCACNA1Fgene of RP was found novel by database searching.Conclusion.By using NGS, we have found a novel heterozygous missense mutation (c.1555C>T, p.R519W) inCACNA1Fgene, which is probably associated with XLRP. The findings might provide new insights into the cause and diagnosis of RP, and have implications for genetic counseling and clinical management in this family.

scholarly journals Novel RB1 and MET Gene Mutations in a Case with Bilateral Retinoblastoma Followed by Multiple Metastatic Osteosarcoma

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Attila Mokánszki ◽  
Yi-Che Chang Chien ◽  
János András Mótyán ◽  
Péter Juhász ◽  
Emese Sarolta Bádon ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Genetic Alterations ◽  
Causative Role ◽  
Rb1 Gene ◽  
Tissue Samples ◽  
Metastatic Osteosarcoma ◽  
Bilateral Retinoblastoma ◽  
Chondroblastic Osteosarcoma ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also a driver for other primary malignancies, which have become the leading cause of death in retinoblastoma survivors. Other malignancies can occur as a consequence of radiotherapy. We describe a patient with retinoblastoma in which we detected a novel RB1 c.2548C > T, p.(Gln850Ter) and a synchronous MET c.3029C > T, p.(Thr1010Ile) mutation as well. After presenting with bilateral retinoblastoma, the patient developed at least four different manifestations of two independent osteosarcomas. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this unique form of retinoblastoma. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia).

scholarly journals Liquid Biopsy Using Ascites and Pleural Effusion Supernatant for Genomic Profiling in Gastrointestinal and Lung Cancers

2021 ◽  
Author(s):  
Hui-Ta Wu ◽  
Hao-Nan Ji ◽  
Wen-Hui Yang ◽  
Min Zhang ◽  
Yi-Fang Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Pleural Effusion ◽  
Mutation Rate ◽  
Gene Mutations ◽  
Specific Gene ◽  
Genomic Profiling ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: Precision medicine highlights the importance of incorporating molecular genetic testing into standard clinical care. Next-generation sequencing (NGS) can detect cancer-specific gene mutations, and molecular targeted drugs can be designed to be effective for one or more specific gene mutations. For patients with special site metastasis, it is particularly important to use appropriate samples for genetic profiling test.Methods: Tissues, plasma, ascites (ASC) supernatants, pleural effusion (PE) samples from gastrointestinal (GI) patients with peritoneal metastasis and lung cancer patients with pleural metastasis were collected for comprehensive genomic profiling. The sample were performed on next-generation sequencing (NGS) using 59 or 1021 cancer-relevant genes panel. Results: The study enrolled 156 tissues, 188 plasma, 45 ascites supernatants, and 1 pleural effusion in 304 GI group and 446 pleural effusion supernatants, 122 tissues, 389 plasma, 45 pleural effusion sediments in 407 lung cancer group. The MSAF were significantly higher in ASC and PE supernatant than plasma ctDNA (50.18% ± 32.03% vs 12.31% ± 19.90%, p < 0.0001 and 33.74% ± 28.34% vs 6.28% ± 12.17%, p < 0.0001, respectively). ASC supernatant had a higher actionable mutation rate than plasma. ASC supernatant accounts for more actionable alterations than plasma ctDNA in 26 paired samples. PE supernatant had higher total actionable mutation rate than plasma (80.3% vs 48.4%, p < 0.05). PE supernatant had a higher frequency of uncommon variations than plasma no matter had distant organ metastasis. Conclusion: ASC and PE supernatants could be better alternatives when tumor tissues are not available in the real world, especially in patients who have only peritoneal or pleural metastases.

scholarly journals Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases

2016 ◽  
Vol 69 (9) ◽  
pp. 767-771 ◽  
Author(s):  
Umberto Malapelle ◽  
Pasquale Pisapia ◽  
Roberta Sgariglia ◽  
Elena Vigliar ◽  
Maria Biglietto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Next Generation ◽  
Genomic Landscape ◽  
Next Generation Sequencing Ngs ◽  
Pcr Targeting ◽  
Diagnostic Setting ◽  
Generation Sequencing

AimsThe incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.MethodsFollowing a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.ResultsA total of 796 somatic mutations in 499 (76.4%) tumours were detected. Besides RAS/RAF/PI3KA and TP53, other 12 genes showed at least one mutation including FBXW7 (6%), PTEN (2.8%), SMAD4 (2.1%), EGFR (1.2%), CTNNB1 (1.1%), AKT1 (0.9%), STK11 (0.8%), ERBB2 (0.6%), ERBB4 (0.6%), ALK (0.2%), MAP2K1 (0.2%) and NOTCH1 (0.2%).ConclusionsIn a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.

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