Molecular Genetics & Genomic Medicine最新文献_第2页

Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities. 全基因组测序在中枢神经系统畸形胎儿产前诊断中的应用

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-10-01 DOI: 10.1002/mgg3.70016

Caiqun Luo, Erya Wen, Yang Liu, Hui Wang, Bei Jia, Liyuan Chen, Xiaoxia Wu, Qian Geng, Huaxuan Wen, Shengli Li, Bingguang Liu, Weiqing Wu, Mei Zhong

{"title":"Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.","authors":"Caiqun Luo, Erya Wen, Yang Liu, Hui Wang, Bei Jia, Liyuan Chen, Xiaoxia Wu, Qian Geng, Huaxuan Wen, Shengli Li, Bingguang Liu, Weiqing Wu, Mei Zhong","doi":"10.1002/mgg3.70016","DOIUrl":"10.1002/mgg3.70016","url":null,"abstract":"Objective: To investigate the clinical value of whole-exome sequencing (WES) in the diagnosis of foetuses with central nervous system (CNS) abnormalities but having a normal karyotyping and chromosomal microarray result.Method: During the period of 2016-2022, there were a total of 149 foetuses with CNS abnormalities but having negative karyotyping and chromosomal microarray analysis results; WES was performed on these foetuses and their parents. Variants were classified according to ACMG guidelines, and the association of pathogenic variants with specific types of CNS abnormalities was explored.Results: Among these 149 foetuses, three categories of abnormalities, namely, single CNS abnormality, multiple CNS abnormalities, CNS abnormalities along with other organ system abnormalities were identified, for which the detection rate of P/LP variants is 17.4% (12/69), 28.6% (14/49) and 54.8% (17/31), respectively.Conclusion: WES brought about an increase of 28.9% in diagnostic yield in the prenatal evaluation of foetuses with CNS abnormalities but having negative karyotyping and chromosome array results. WES may also be of benefit for the diagnosis of foetuses with isolated CNS abnormalities, as well as for making more informed interpretations of imaging findings and for providing better genetic counselling.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CANVAR: A Tool for Clinical Annotation of Variants Using ClinVar Databases. CANVAR：使用 ClinVar 数据库对变异进行临床注释的工具。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-10-01 DOI: 10.1002/mgg3.70020

Lau K Vestergaard, Joanna Lopacinska-Jørgensen, Estrid V Høgdall

{"title":"CANVAR: A Tool for Clinical Annotation of Variants Using ClinVar Databases.","authors":"Lau K Vestergaard, Joanna Lopacinska-Jørgensen, Estrid V Høgdall","doi":"10.1002/mgg3.70020","DOIUrl":"10.1002/mgg3.70020","url":null,"abstract":"Background: Genomic medicine has transformed clinical genetics by utilizing high-throughput sequencing technologies to analyze genetic variants associated with diseases. Accurate variant classification is crucial for diagnosis and treatment decisions, and various tools and software such as the Ion Reporter Software and the Illumina Nirvana Software often used in a clinical setting utilize information from the ClinVar database/archive to aid in variant interpretation. However, these existing annotation tools may lack access to the latest ClinVar data, necessitating manual variant inspection.Aims: To address this gap in developing a tool providing the latest ClinVar data for variant annotation in clinical and research settings.Materials and methods: We introduce CANVAR, a Python-based script that efficiently annotates variants identified from next-generation sequencing in a clinical or research context, offering comprehensive information from the latest ClinVar database.Results: CANVAR provides accurate, up-to-date variant annotations, streamlining variant analysis.Discussion: The rise in genomic data requires accurate variant annotation for clinical decision-making. Misclassification poses risks, and current tools may not always access the latest data, challenging variant interpretation.Conclusion: CANVAR contributes to enhancing variant annotation by offering comprehensive information from the latest ClinVar database for genetic variants identified through next-generation sequencing.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a RAD21 Variant 与 RAD21 变异相关的科尼莉亚-德-朗格综合征 4 型的临床特征、遗传分析和文献综述

IF 2 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-17 DOI: 10.1002/mgg3.70009

Xinyu Yue, Meiping Chen, Xiaoan Ke, Hongbo Yang, Fengying Gong, Linjie Wang, Lian Duan, Hui Pan, Huijuan Zhu

{"title":"Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a RAD21 Variant","authors":"Xinyu Yue, Meiping Chen, Xiaoan Ke, Hongbo Yang, Fengying Gong, Linjie Wang, Lian Duan, Hui Pan, Huijuan Zhu","doi":"10.1002/mgg3.70009","DOIUrl":"https://doi.org/10.1002/mgg3.70009","url":null,"abstract":"BackgroundCornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants.MethodsA patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole‐exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing.ResultsA 13.3‐year‐old male patient with a height of 136.5 cm (−3.5 SDS) and a weight of 28.4 kg (−3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients.ConclusionThis study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The genetic analysis of eight families with hemophilia B in Mongolia: Identification of two novel mutation 对蒙古八个 B 型血友病家庭的基因分析：发现两种新型基因突变

IF 2 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-13 DOI: 10.1002/mgg3.2495

Purevdorj Munkhuu, Munkhtsetseg Bazarragchaa, Purevdorj Ichinkhorloo, Ki‐Young Yoo, Enkh‐Amar Ayush, Ochbadrakh Batjargal, Erdenebayar Namjil, Sarantuya Jav, Erkhembulgan Purevdorj, Sodnomtsogt Lkhagvasuren

{"title":"The genetic analysis of eight families with hemophilia B in Mongolia: Identification of two novel mutation","authors":"Purevdorj Munkhuu, Munkhtsetseg Bazarragchaa, Purevdorj Ichinkhorloo, Ki‐Young Yoo, Enkh‐Amar Ayush, Ochbadrakh Batjargal, Erdenebayar Namjil, Sarantuya Jav, Erkhembulgan Purevdorj, Sodnomtsogt Lkhagvasuren","doi":"10.1002/mgg3.2495","DOIUrl":"https://doi.org/10.1002/mgg3.2495","url":null,"abstract":"BackgroundThis study aimed to conduct molecular diagnostics among individuals with hemophilia B (HB) and carriers of hemophilia in Mongolia.MethodsEight patients (six severe, two mild) with HB and their 12 female relatives were enrolled from eight families. Sanger sequence was performed for mutation identification. The questionnaire survey was conducted to evaluate carrier symptoms in female relatives.ResultsTwo families had a history of HB. A total of five different variants (c.223C > T; c.344A > G; c.464G > C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C > T (p.Arg75*) mutation was detected in two unrelated patients. Carrier testing identified five mothers as carriers, while one younger sister was a non‐carrier. The carrier status of six female relatives of the two mild patients remained undetermined. By questionnaire survey, only one of the five genetically identified carriers displayed noticeable symptoms of being a carrier.ConclusionThe novel variants c.187_188del and c.1314_1314delA can cause severe hemophilia B. This study did not observe a significant association between symptoms and carrier status in the five carriers.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of the Haematological Phenotype and Molecular Characteristics of Rare Abnormal Haemoglobin 罕见异常血红蛋白的血液学表型和分子特征分析

IF 2 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-12 DOI: 10.1002/mgg3.70012

Yanfen Ge, Guansheng Zheng, Luhua Xian, Yanfei Luo, Junru Liu, Ting Lin, Wenhao Cui, Yujing Yang, Huizhuang Shan

{"title":"Analysis of the Haematological Phenotype and Molecular Characteristics of Rare Abnormal Haemoglobin","authors":"Yanfen Ge, Guansheng Zheng, Luhua Xian, Yanfei Luo, Junru Liu, Ting Lin, Wenhao Cui, Yujing Yang, Huizhuang Shan","doi":"10.1002/mgg3.70012","DOIUrl":"https://doi.org/10.1002/mgg3.70012","url":null,"abstract":"BackgroundHaemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China.MethodsPeripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High‐performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing.ResultsThe research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg.ConclusionWe confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142188672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incorporating Next-Generation Sequencing as a Second-Tier Test for Primary Carnitine Deficiency. 将新一代测序技术作为原发性肉碱缺乏症的二级检测方法。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70003

Yiming Lin, Zhenzhu Zheng, Weihua Lin, Weilin Peng

{"title":"Incorporating Next-Generation Sequencing as a Second-Tier Test for Primary Carnitine Deficiency.","authors":"Yiming Lin, Zhenzhu Zheng, Weihua Lin, Weilin Peng","doi":"10.1002/mgg3.70003","DOIUrl":"10.1002/mgg3.70003","url":null,"abstract":"Background: Newborn screening (NBS) for primary carnitine deficiency (PCD) has poor performance. This study aimed to evaluate the feasibility of incorporating next-generation sequencing (NGS) as a second-tier PCD test.Methods: Between March and December 2020, 60,070 newborns were screened for inherited metabolic disorders. Newborns with free carnitine (C0) levels below 8.5 μmol/L were selected for second-tier genetic testing.Results: In total, 130 (0.22%) newborns with low C0 levels underwent second-tier genetic testing, 87 (66.92%) had positive genetic testing results, and 30 (23.08%) carried pathogenic variants of the SLC22A5 gene. Six newborns were diagnosed with PCD. The incidence of PCD was approximately 1 in 1:10,012 newborns. The PPV reached 20% after combining with second-tier NGS. Of the eight variants identified in patients with PCD, the three most common variants were c.760C>T (p.Arg254*), c.51C>G (p.Phe17Leu), and c.1400C>G (p.Ser467Cys). The C0 levels of patients with PCD were significantly lower than those of PCD carriers (p = 0.0026) and PCD-negative individuals (p = 0.0005).Conclusions: Our results showed that the PPV reached 20% after combining with second-tier NGS. The MS/MS-based NBS and second-tier NGS combination can effectively reduce the false-positive rate and detect PCD in patients.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proximal 4p Deletion Syndrome in an Infant With Multiple Systemic Anomalies. 伴有多系统畸形的婴儿近端 4p 缺失综合征

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70005

Ying Pang, Lan Zeng, Hua Liang, Chunlan Cheng, Lihui Shan, Jin Wang, Nanjing Jiang, Guanghuan Pi, Li Yang, Ai Chen, Fu Xiong, Shuyao Zhu

{"title":"Proximal 4p Deletion Syndrome in an Infant With Multiple Systemic Anomalies.","authors":"Ying Pang, Lan Zeng, Hua Liang, Chunlan Cheng, Lihui Shan, Jin Wang, Nanjing Jiang, Guanghuan Pi, Li Yang, Ai Chen, Fu Xiong, Shuyao Zhu","doi":"10.1002/mgg3.70005","DOIUrl":"10.1002/mgg3.70005","url":null,"abstract":"Background: Contiguous gene deletion in the short arm of chromosome 4 is linked to various neurodevelopmental disorders.Methods: In this study, we conducted peripheral blood chromosome G-banding karyotyping and whole-exome sequencing (WES) on a proband presenting with anal atresia, global developmental delay, lymphocytosis, and other multisystem anomalies. Additionally, chromosome G-banding karyotyping was also carried out on the proband's parents and brother.Results: The 7-month-old proband was found to have a 26.738 Mb 4p15.33-p14 deletion as identified by chromosome G-banding karyotyping and WES.Conclusion: We identified a patient with proximal 4p deletion syndrome by karyotype and WES analysis, which might explain some of his phenotypes. Our research enhances clinicians' knowledge of this rare condition, and offers valuable genetic counseling to the affected family. Further research is necessary to identify the causative gene or critical region associated with proximal 4p deletion syndrome.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frameshift Mutation in PAX2 Related to Focal Segmental Glomerular Sclerosis: A Case Report and Literature Review. 与局灶性肾小球硬化症有关的 PAX2 基因框变突变：病例报告和文献综述

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70006

Xueling Hu, Wei Lin, Zengyuan Luo, Yong Zhong, Xiangcheng Xiao, Rong Tang

{"title":"Frameshift Mutation in PAX2 Related to Focal Segmental Glomerular Sclerosis: A Case Report and Literature Review.","authors":"Xueling Hu, Wei Lin, Zengyuan Luo, Yong Zhong, Xiangcheng Xiao, Rong Tang","doi":"10.1002/mgg3.70006","DOIUrl":"10.1002/mgg3.70006","url":null,"abstract":"Background: Paired box gene 2 (PAX2) heterozygous mutations can cause renal coloboma syndrome, but its role in patients with focal segmental glomerular sclerosis (FSGS) has been rarely reported.Methods: Based on the clinical manifestations and renal pathological characteristics of the patient, as well as familial whole exome sequencing, the diagnosis of FSGS related to PAX2 mutation was confirmed. Treatment such as lowering urinary protein and blood pressure was given, and the patient was followed up and observed.Results: There is a familial heterozygous case presented with chronic kidney disease secondary to FSGS, which was related to PAX2 frameshift mutation due to the deletion of G at the position 76 (c.76delG). To our knowledge, this is the first report of PAX2 c.76delG variant related to adult-onset FSGS.Conclusion: Here, we further expand the phenotypic spectrum of FSGS. Genetic screening especially PAX2 mutation is recommended in patients with adult-onset FSGS of unknown etiology.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome. 一种新型杂合子非线性 FBN1 变体导致马凡氏综合征的 RNA 剪接异常。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70004

Djouhayna Dougarem, Yi-Xiao Chen, Yi-Na Sun, He-Feng Huang, Qiong Luo

{"title":"A Novel Heterozygous Intronic FBN1 Variant Contributes to Aberrant RNA Splicing in Marfan Syndrome.","authors":"Djouhayna Dougarem, Yi-Xiao Chen, Yi-Na Sun, He-Feng Huang, Qiong Luo","doi":"10.1002/mgg3.70004","DOIUrl":"10.1002/mgg3.70004","url":null,"abstract":"Background: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene.Methods: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father.Results: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful.Conclusion: This research identified a novel intronic pathogenic FBN1: c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M).","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optical Genome Mapping Identifies a Second Xq27.1 Rearrangement Associated With Charcot-Marie-Tooth Neuropathy CMTX3. 光学基因组图谱发现与夏科-玛丽齿神经病 CMTX3 有关的第二个 Xq27.1 重排。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70014

Elisa Rahikkala, Jonna Komulainen-Ebrahim, Jussi-Pekka Tolonen, Sandra Vorimo, Maria Suo-Palosaari, Päivi Vieira, Johanna Piispala, Johanna Uusimaa, Katri Pylkäs, Tuomo Mantere

{"title":"Optical Genome Mapping Identifies a Second Xq27.1 Rearrangement Associated With Charcot-Marie-Tooth Neuropathy CMTX3.","authors":"Elisa Rahikkala, Jonna Komulainen-Ebrahim, Jussi-Pekka Tolonen, Sandra Vorimo, Maria Suo-Palosaari, Päivi Vieira, Johanna Piispala, Johanna Uusimaa, Katri Pylkäs, Tuomo Mantere","doi":"10.1002/mgg3.70014","DOIUrl":"https://doi.org/10.1002/mgg3.70014","url":null,"abstract":"Background: X-linked recessive type 3 Charcot-Marie-Tooth (CMTX3) is a rare subtype of childhood-onset CMT. To date, all reported CMTX3 patients share a common founder 78 kb insertion from chromosome 8 into the Xq27.1 palindrome region.Methods: We conducted patient-parent trio optical genome mapping (OGM) on a male patient presenting with clinically diagnosed Dejerine-Sottas disease for whom initial standard diagnostic genetic tests, including whole-genome sequencing (WGS), yielded negative results.Results: OGM analysis revealed a maternally inherited interchromosomal insertion from chromosome region 7q31.1 into Xq27.1. Coupled with manual reassessment of WGS data, this confirmed the molecular diagnosis of atypical CMTX3 and showed that the 122.4 kb inserted fragment contained DLD and partially LAMB1. Subsequent analyses confirmed that the rearrangement had arisen de novo in the proband's mother.Conclusion: We report the second Xq27.1 rearrangement associated with CMTX3, providing novel clinical insights into its phenotypic and genotypic spectrum. Our findings highlight the importance of including genomic rearrangement analysis of Xq27.1 in standard diagnostic pipelines for childhood-onset CMT. Given the overlap in polyneuropathy phenotypes resulting from insertions from chromosomes 7 and 8 into the same Xq27.1 palindrome region, the pathogenic mechanism underlying peripheral neuropathy in CMTX3 likely involves dysregulation of genes within this region.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0