scholarly journals Three novel mutations of microphthalmos identified in two Chinese families

2020 ◽  
Author(s):  
Yating Tang ◽  
Jie Xu ◽  
Tianyu Zheng ◽  
Yi Lu
Keyword(s):  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Novel Mutations ◽  
Chinese Families ◽  
Target Capture ◽  
Disease Related Genes ◽  
Presymptomatic Diagnosis ◽  
Target Capture Sequencing ◽  
Generation Sequencing

Abstract Background: To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families.Methods: In our study, we screened 425 potential eye disease-related genes of the proband of a three-generation Chinese family diagnosed with microphthalmos using next-generation sequencing-based target capture sequencing. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation.Results: We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, PXDN c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and CRYBB2 c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation.Conclusions: The three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early presymptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

scholarly journals Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis

2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Keiko Shimojima Yamamoto ◽  
Taiju Utshigisawa ◽  
Hiromi Ogura ◽  
Takako Aoki ◽  
Takahiro Kawakami ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Hereditary Spherocytosis ◽  
Genetic Diagnosis ◽  
Genomic Analysis ◽  
Japanese Patients ◽  
Asian Countries ◽  
Target Capture ◽  
Detailed Family History ◽  
Target Capture Sequencing ◽  
Chronic Hemolytic Anemia

AbstractHereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.

Genetic diagnosis of Hailey–Hailey disease in two Chinese families: novel mutations in theATP2C1gene

2009 ◽  
Vol 34 (8) ◽  
pp. e968-e971 ◽  
Author(s):  
Y. G. Ding ◽  
H. Fang ◽  
L. M. Lao ◽  
X. J. Jiang ◽  
H. C. Chen
Keyword(s):  
Genetic Diagnosis ◽  
Novel Mutations ◽  
Chinese Families

scholarly journals Target Capture Sequencing of SARS-CoV-2 Genomes Using the ONETest Coronaviruses Plus

2021 ◽  
Author(s):  
Shing H. Zhan ◽  
Sepideh M. Alamouti ◽  
Brian S. Kwok ◽  
Meng-Hsun Lee ◽  
Jaswinder Khattra ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Added Value ◽  
Respiratory Pathogens ◽  
Sequence Coverage ◽  
Pcr Assay ◽  
Genetic Changes ◽  
Target Capture ◽  
Archived Samples ◽  
Target Capture Sequencing ◽  
Generation Sequencing

ABSTRACTBackgroundGenomic sequencing is important to track and monitor genetic changes in SARS-CoV-2. We introduce a target capture next-generation sequencing methodology, the ONETest Coronaviruses Plus, to sequence SARS-CoV-2 genomes and select genes of other respiratory viruses simultaneously.MethodsWe applied the ONETest on 70 respiratory samples (collected in Florida, USA between May and July, 2020), in which SARS-CoV-2 had been detected by a qualitative PCR assay. For 48 (69%) of the samples, we also applied the ARTIC protocol for Illumina sequencing. All the libraries were sequenced as 2×150 nucleotide reads on an Illumina instrument. The ONETest data were analyzed using an in-house pipeline and the ARTIC data using a published pipeline to produce consensus SARS-CoV-2 genome sequences, to which lineages were assigned using pangolin.ResultsOf the 70 ONETest libraries, 45 (64%) had a complete or near-complete SARS-CoV-2 genome sequence (> 29,000 bases and with > 90% of its bases covered by at least 10 reads). Of the 48 ARTIC libraries, 25 (52%) had a complete or near-complete SARS-CoV-2 genome sequence.In 24 out of 34 (71%) samples in which both the ONETest and ARTIC sequences were complete or near-complete and in which lineage could be assigned to both the ONETest and ARTIC sequences, the SARS-CoV-2 lineage identified was the same.ConclusionsThe ONETest can be used to sequence the SARS-CoV-2 genomes in archived samples and thereby enable detection of circulating and emerging SARS-CoV-2 variants. Target capture approaches, such as the ONETest, are less prone to loss of sequence coverage probably due to amplicon dropouts encountered in amplicon approaches, such as ARTIC. With its added value of characterizing other major respiratory pathogens, although not assessed in this study, the ONETest can help to better understand the epidemiology of infectious respiratory disease in the post COVID-19 era.

scholarly journals Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Juan Wu ◽  
Lijia Chen ◽  
Oi Sin Tam ◽  
Xiu-Feng Huang ◽  
Chi-Pui Pang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Direct Sequencing ◽  
Genetic Defect ◽  
Chinese Family ◽  
Next Generation ◽  
Whole Exome ◽  
Generation Sequencing

Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP), the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.

scholarly journals Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shan Li ◽  
Jianfei Zhang ◽  
Yixuan Cao ◽  
Yi You ◽  
Xiuli Zhao
Keyword(s):  
Next Generation Sequencing ◽  
Congenital Cataract ◽  
Bioinformatics Analysis ◽  
Next Generation ◽  
Novel Mutations ◽  
Congenital Cataracts ◽  
Chinese Families ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background Congenital cataract is a clinically and genetically heterogeneous visual impairment. The aim of this study was to identify causative mutations in five unrelated Chinese families diagnosed with congenital cataracts. Methods Detailed family history and clinical data were collected, and ophthalmological examinations were performed using slit-lamp photography. Genomic DNA was extracted from peripheral blood of all available members. Thirty-eight genes associated with cataract were captured and sequenced in 5 typical nonsyndromic congenital cataract probands by targeted next-generation sequencing (NGS), and the results were confirmed by Sanger sequencing. Bioinformatics analysis was performed to predict the functional effect of mutant genes. Results Results from the DNA sequencing revealed five potential causative mutations: c.154 T > C(p.F52 L) in GJA8 of Family 1, c.1152_1153insG(p.S385Efs*83) in GJA3 of Family 2, c.1804 G > C(p.G602R) in BFSP1 of Family 3, c.1532C > T(p.T511 M) in EPHA2 of Family 4 and c.356G > A(p.R119H) in HSF4 of Family 5. These mutations co-segregated with all affected individuals in the families and were not found in unaffected family members nor in 50 controls. Bioinformatics analysis from several prediction tools supported the possible pathogenicity of these mutations. Conclusions In this study, we identified five novel mutations (c.154 T > C in GJA8, c.1152_1153insG in GJA3, c.1804G > C in BFSP1, c.1532C > T in EPHA2, c.356G > A in HSF4) in five Chinese families with hereditary cataracts, respectively. NGS can be used as an effective tool for molecular diagnosis of genetically heterogeneous disorders such as congenital cataract, and the results can provide more effective clinical diagnosis and genetic counseling for the five families.

scholarly journals Five Novel Mutations in LOXHD1 Gene Were Identified to Cause Autosomal Recessive Nonsyndromic Hearing Loss in Four Chinese Families

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaohui Bai ◽  
Chi Zhang ◽  
Fengguo Zhang ◽  
Yun Xiao ◽  
Yu Jin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Corneal Dystrophy ◽  
Underlying Mechanism ◽  
Nonsyndromic Hearing Loss ◽  
Novel Mutations ◽  
Chinese Families ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing ◽  
Autosomal Recessive Pattern

Hearing loss is one of the most common sensory disorders in newborns and is mostly caused by genetic factors. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is usually characterized as a severe-to-profound congenital sensorineural hearing loss and later can cause various degrees of defect in the language and intelligent development of newborns. The mutations in LOXHD1 gene have been shown to cause DFNB77, a type of ARNSHL. To date, there are limited reports about the association between LOXHD1 gene and ARNSHL. In this study, we reported six patients from four Chinese families suffering from severe-to-profound nonsyndromic hearing loss. We performed targeted next generation sequencing in the six affected members and identified five novel pathogenic mutations in LOXHD1 including c.277G>A (p.D93N), c.611-2A>T, c.1255+3A>G, c.2329C>T (p.Q777∗), and c.5888delG (p.G1963Afs∗136). These mutations were confirmed to be cosegregated with the hearing impairment in the families by Sanger sequencing and were inherited in an autosomal recessive pattern. All of the five mutations were absent in 200 control subjects. There were no symptoms of Fuchs corneal dystrophy in the probands and their blood-related relatives. We concluded that these five novel mutations could be involved in the underlying mechanism resulting in the hearing loss, and this discovery expands the genotypic spectrum of LOXHD1 mutations.

scholarly journals Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families

2018 ◽  
Author(s):  
Zhenyu Wang ◽  
Chen Huang ◽  
Yanxiu Sun ◽  
Huibin Lv ◽  
Mingzhou Zhang ◽  
...  
Keyword(s):  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Bioinformatics Analysis ◽  
Genetic Defect ◽  
Hereditary Disease ◽  
The Other ◽  
Novel Mutations ◽  
Chinese Families ◽  
Functional Changes ◽  
Autosomal Dominant Congenital Cataract

AbstractPurposeAs the leading cause of the impairment of vision of children, congenital cataract is considered as a hereditary disease, especially autosomal dominant congenital cataract (ADCC). The purpose of this study is to identify the genetic defect of six Chinese families with ADCC.Subjects and MethodsSix Chinese families with ADCC were recruited in the study. (103 members in total, 96 members alive, 27 patients in total) Genomic DNA samples extracting from probands’ peripheral blood cells were captured the mutations using a specific eye disease enrichment panel with next generation sequencing. After initial pathogenicity prediction, sites with specific pathogenicity were screened for further validation. Sanger sequencing was conducted in the other individuals in the families and other 100 normal controls. Mutations definitely related with ADCC will then be analyzed by bioinformatics analysis. The pathogenic effect of the amino acid changes and structural and functional changes of the proteins were finally analyzed by bioinformatics analysis.ResultsSeven mutations in six candidate genes associated with ADCC of six families were detected (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A, WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). All the seven mutations were only detected on affected individuals in the families. Among them there are three novel mutations (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A) and four that have been reported (WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). RPGRIP1 (c.2669G>A) mutation and CRYBA4 (c.26C>T) mutation are predicted to be benign according to bioinformatics analysis while the other five mutations (EPHA2, PAX6, MYH9, CRYBA4 c.169T>C, WFS1) are thought to be pathogenic.ConclusionWe report two novel heterozygous mutations (MYH9 c.4150G>C and CRYBA4 c.169T>C) in six Chinese families supporting their vital roles in causing ADCC.

scholarly journals A Novel Mutation in the Kringle IV Domain of LPA gene leading to Familial Hyperlipoproteinemia

2019 ◽  
Author(s):  
Youran Li ◽  
Xinyue Zhang ◽  
Yizhong Wang ◽  
Fan Gong ◽  
Xiaofei Yu ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Chinese Family ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Combined Use ◽  
The Family ◽  
Number Variation ◽  
Generation Sequencing

Abstract Background This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese Han family with hyperlipoproteinemia. Methods The combined use of next-generation sequencing and qPCR technique was performed to investigate genetic pathology of familial hyperlipoproteinemia. Results The clinical manifestations of the family members include hyperlipoproteinemia, early-onset hypertension, coronary heart disease, lipoma, cerebral infarction and even sudden death, and a novel heterozygous deletion of 3-16 exon of LPA gene was identified to be causative for the symptoms in the family. Conclusions A novel deletion in the LPA gene was identified in a Chinese family associated with hyperlipoproteinemia, which expands the spectrum of the LPA mutation and its associated phenotype. Keywords Copy number variation; Hyperlipoproteinemia; Kringle IV; Lipoprotein(a); LPA;

scholarly journals High Diagnostic Yield of Targeted Next-Generation Sequencing in a Cohort of Patients With Congenital Hypothyroidism Due to Dyshormonogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Athanasia Stoupa ◽  
Ghada Al Hage Chehade ◽  
Rim Chaabane ◽  
Dulanjalee Kariyawasam ◽  
Gabor Szinnai ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Congenital Hypothyroidism ◽  
Diagnostic Yield ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Compound Heterozygous ◽  
Next Generation ◽  
Hormone Production ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

ObjectiveTo elucidate the molecular cause in a well-characterized cohort of patients with Congenital Hypothyroidism (CH) and Dyshormonogenesis (DH) by using targeted next-generation sequencing (TNGS).Study designWe studied 19 well-characterized patients diagnosed with CH and DH by targeted NGS including genes involved in thyroid hormone production. The pathogenicity of novel mutations was assessed based on in silico prediction tool results, functional studies when possible, variant location in important protein domains, and a review of the recent literature.ResultsTNGS with variant prioritization and detailed assessment identified likely disease-causing mutations in 10 patients (53%). Monogenic defects most often involved TG, followed by DUOXA2, DUOX2, and NIS and were usually homozygous or compound heterozygous. Our review shows the importance of the detailed phenotypic description of patients and accurate analysis of variants to provide a molecular diagnosis.ConclusionsIn a clinically well-characterized cohort, TNGS had a diagnostic yield of 53%, in accordance with previous studies using a similar strategy. TG mutations were the most common genetic defect. TNGS identified gene mutations causing DH, thereby providing a rapid and cost-effective genetic diagnosis in patients with CH due to DH.

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