Molecular Genetics & Genomic Medicine最新文献_第4页

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":"26 1","pages":""},"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":"69 1","pages":"e70012"},"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

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":"12 9","pages":"e70005"},"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

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":"12 9","pages":"e70003"},"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

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":"12 9","pages":"e70006"},"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":"12 9","pages":"e70004"},"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":"12 9","pages":"e70014"},"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

Identification of rare missense variants in the BSN gene co-segregating with chronic otitis media in a consanguineous Pakistani family. 在一个巴基斯坦近亲家庭中发现与慢性中耳炎共存的 BSN 基因罕见错义变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.2478

Ayesha Yousaf, Sairah Yousaf, Asra S Shabbir, Rafia Yousaf, Saima Riazuddin, Rehan S Shaikh, Regie Lyn P Santos-Cortez, Zubair M Ahmed

{"title":"Identification of rare missense variants in the BSN gene co-segregating with chronic otitis media in a consanguineous Pakistani family.","authors":"Ayesha Yousaf, Sairah Yousaf, Asra S Shabbir, Rafia Yousaf, Saima Riazuddin, Rehan S Shaikh, Regie Lyn P Santos-Cortez, Zubair M Ahmed","doi":"10.1002/mgg3.2478","DOIUrl":"10.1002/mgg3.2478","url":null,"abstract":"Background: Otitis media (OM) is the most frequent and complex middle ear condition with multifactorial etiology including genetic predisposition. OM depicts a variable clinical spectrum, leading to speech, developmental delay, and hearing loss. Here, we report the clinical and genetic findings of chronic suppurative otitis media (CSOM) segregating in a six-generation consanguineous Pakistani family PKOM08.Methods: Clinical evaluations, including audio and tympanometry, were conducted to assess OM manifestation and their impact on hearing function. Exome sequencing was performed to identify potential genetic variants underlying CSOM in the study participants.Results: Clinical evaluation of participating individuals revealed varying degrees of disease severity, with mild to moderate hearing loss. All the affected individuals had CSOM with no other apparent comorbidity. Whole exome followed by Sanger sequencing revealed two rare heterozygous variants [c.1867C>T, p.(Pro623Ser) and c.11015G>A, p.(Arg3672Gln)] of BSN gene in most of the affected individuals of family PKOM08. BSN encodes a scaffold bassoon protein involved in synaptic vesicle trafficking. The identified variants replaced evolutionary conserved amino acid residues in the encoded protein and are predicted to impact the ionic interactions in the secondary structure.Conclusion: A deep intronic variant of BSN has been previously implicated in the etiology of childhood ear infections. Our study further supports a link between BSN-impaired function and ear infection and CSOM in children.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 9","pages":"e2478"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291531","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

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70010

Rebecca Finnegan, Mary O'Regan, Máire White, Gianpiero L Cavalleri, Norman Delanty, Katherine A Benson, Marie T Greally

{"title":"Similarity of Phenotype in Three Male Patients With the c.320A>G Variant in ALG13: Possible Genotype-Phenotype Correlation.","authors":"Rebecca Finnegan, Mary O'Regan, Máire White, Gianpiero L Cavalleri, Norman Delanty, Katherine A Benson, Marie T Greally","doi":"10.1002/mgg3.70010","DOIUrl":"10.1002/mgg3.70010","url":null,"abstract":"Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG-1 syndromes, most of which are inherited as autosomal recessive traits, although X-linked inheritance has also been reported. Pathogenic variants in the asparagine-linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date.Methods: We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant.Results: All three males have a de novo mutation, infantile spasms, DEE, drug-resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13.Conclusion: The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype-phenotype correlation.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 9","pages":"e70010"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291533","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 Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis. 麦克劳德综合征和舞蹈症-黄细胞增多症中国患者的临床特征和新的致病变异。

IF 1.5 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2024-09-01 DOI: 10.1002/mgg3.70015

Hao Yu, Ling Li, Xiaoyan Li, Haipeng Liu

{"title":"Clinical Features and Novel Pathogenic Variants of Chinese Patients With McLeod Syndrome and Chorea-Acanthocytosis.","authors":"Hao Yu, Ling Li, Xiaoyan Li, Haipeng Liu","doi":"10.1002/mgg3.70015","DOIUrl":"10.1002/mgg3.70015","url":null,"abstract":"Background: McLeod syndrome (MLS) and chorea-acanthocytosis (ChAc) are exceedingly rare diseases characterized by a variety of movement disorders including chorea, dystonia, and Parkinsonism. Genetic analysis plays a key role in early and accurate diagnosis, but relevant variants are still under investigation. This study aims to explore new pathogenic variants in Chinese patients with MLS and ChAc and to conduct a comprehensive analysis of the clinical heterogeneity among these patients.Methods: Eighteen Chinese patients who presented with choreatic movements with negative HTT genetic testing were identified and underwent targeted next-generation sequencing, verified by Sanger sequencing.Results: Two novel XK variants (c.970A>T, c.422_423del) were identified in three index MLS patients and six novel VPS13A variants (c.9219C>A, c.3467T>A, c.4208dup, c.9243_9246del, c.5364del, c.556-290_697-483del) in five index ChAc patients. One copy number variant of VPS13A (g.79827595_79828762del/c.556-290_697-483del) was firstly described in Chinese population.Conclusion: As the currently largest descriptive study of MLS and ChAc patients in China, this study expands on the clinical and genetic spectrum of XK and VPS13A, contributing to the clinical diagnosis of MLS and ChAc.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 9","pages":"e70015"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350296","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