Case Reports in Genetics最新文献_第2页

Quadruple Primary Malignancies over 2 Years with Germline Mutation in Krebs Cycle Enzyme Gene Fumarate Hydratase. 克雷布斯循环酶基因富马酸氢化酶的种系突变导致两年内四次原发性恶性肿瘤。

Case Reports in Genetics Pub Date : 2024-06-06 eCollection Date: 2024-01-01 DOI: 10.1155/2024/5591237

Solaleh Aminian, Fawaz Al-Alloosh, Fatemeh Yadegari, Shiva Zarinfam, Haider Hamza Al-Abedi, Keivan Majidzadeh-A

{"title":"Quadruple Primary Malignancies over 2 Years with Germline Mutation in Krebs Cycle Enzyme Gene Fumarate Hydratase.","authors":"Solaleh Aminian, Fawaz Al-Alloosh, Fatemeh Yadegari, Shiva Zarinfam, Haider Hamza Al-Abedi, Keivan Majidzadeh-A","doi":"10.1155/2024/5591237","DOIUrl":"10.1155/2024/5591237","url":null,"abstract":"Multiple primary cancers (MPCs) are defined as the presence of more than one cancer in an individual that is not due to recurrence, metastasis, or local spread. Different factors such as copathogenic genetic mutations, environmental factors, lifestyle, and first cancer treatment increase the possible occurrence of subsequent malignancies. In recent years, the risk of MPCs has increased due to improved treatment; however, quadruple primary malignancies are still rare and require further investigation and treatment of the underlying cause. Here, we present a 64-year-old man with a 40-year history of cigarette smoking who developed quadruple primary malignancies of the epiglottis, kidney, pancreas, and lung. To investigate the possible genetic cause, we performed WES, and a variant of c.580G > A (Ala194Thr) was discovered in exon 5 of the Krebs cycle enzyme gene, fumarate hydratase (FH). This substitution was classified as VUS in Clinvar and likely pathogenic by Varsome and Franklin software. The structural analysis showed that the variation found was localized in a highly conserved alpha helix in the D2 domain near the FH hinge region (<6 Å), suggesting that enzyme activity was affected by a perturbation in protein quaternary structure. Because of the well-established role of FH mutations in renal cancer risk, it was possible that the FH mutation could have led to the development of renal cell carcinoma in this case. The biological mechanisms of MPCs suggest that subsequent primary malignancies are triggered by the combined effects of environmental factors, such as smoking and genetics.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"5591237"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus 在一名由爱泼斯坦-巴氏病毒（Epstein-Barr Virus）引发的肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）的白种女性患者中发现线粒体 DNA 错义突变 ChrMT: 8981A > G 和 ChrMT: 6268C > T

Case Reports in Genetics Pub Date : 2024-05-09 DOI: 10.1155/2024/6475425

Gaoyan G. Tang-Siegel, David W. Maughan, Milah B. Frownfelter, Alan R. Light

{"title":"Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus","authors":"Gaoyan G. Tang-Siegel, David W. Maughan, Milah B. Frownfelter, Alan R. Light","doi":"10.1155/2024/6475425","DOIUrl":"https://doi.org/10.1155/2024/6475425","url":null,"abstract":"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue. Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein–Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman. A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP. Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient's mitochondria and the development of her ME/CFS symptoms.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus. 在一名由 Epstein-Barr 病毒引发的肌痛性脑脊髓炎/慢性疲劳综合征 (ME/CFS) 的白种女性患者中发现线粒体 DNA 错义突变 ChrMT: 8981A > G 和 ChrMT: 6268C > T。

Case Reports in Genetics Pub Date : 2024-05-09 eCollection Date: 2024-01-01 DOI: 10.1155/2024/6475425

Gaoyan G Tang-Siegel, David W Maughan, Milah B Frownfelter, Alan R Light

{"title":"Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus.","authors":"Gaoyan G Tang-Siegel, David W Maughan, Milah B Frownfelter, Alan R Light","doi":"10.1155/2024/6475425","DOIUrl":"https://doi.org/10.1155/2024/6475425","url":null,"abstract":"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue. Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein-Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman. A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP. Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient's mitochondria and the development of her ME/CFS symptoms.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"6475425"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bilateral Glaucoma as Possible Additional Feature for PGAP3-Associated Hyperphosphatasia 双侧青光眼可能是 PGAP3 相关性高磷血症的附加特征

Case Reports in Genetics Pub Date : 2024-03-23 DOI: 10.1155/2024/3561555

Osama Obaid, Reem Batawi, Heba Alqurashi, Thana Ewis, A. A. Obaid

引用次数: 0

Constitutional Chromothripsis on Chromosome 2: A Rare Case with Severe Presentation. 2 号染色体上的宪制性染色体三分裂症：一个表现严重的罕见病例。

Case Reports in Genetics Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1155/2024/6319030

Afia Hasnain, Laura L Thompson, Nicole L Hoppman, Karine Hovanes, Jing Liu, Bita Hashemi

{"title":"Constitutional Chromothripsis on Chromosome 2: A Rare Case with Severe Presentation.","authors":"Afia Hasnain, Laura L Thompson, Nicole L Hoppman, Karine Hovanes, Jing Liu, Bita Hashemi","doi":"10.1155/2024/6319030","DOIUrl":"10.1155/2024/6319030","url":null,"abstract":"Chromothripsis is characterized by shattering and subsequent reassembly of chromosomes by DNA repair processes, which can give rise to a variety of congenital abnormalities and cancer. Constitutional chromothripsis is a rare occurrence, reported in children presenting with a wide range of birth defects. We present a case of a female child born with multiple major congenital abnormalities including severe microcephaly, ocular dysgenesis, heart defect, and imperforate anus. Chromosomal microarray and mate pair sequencing identified a complex chromosomal rearrangement involving the terminal end of the long arm of chromosome 2, with two duplications (located at 2p25.3-p25.1 and 2q35-q37.2 regions) and two deletions (located at 2q37.2-q37.3 and 2q37.3 regions) along with structural changes including inverted segments. A review of the literature for complex rearrangements on chromosome 2 revealed overlapping features; however, our patient had a significantly more severe phenotype which resulted in early death at the age of 2 years. Breakpoints analysis did not reveal the involvement of any candidate genes. We concluded that the complexity of the genomic rearrangement and the combined dosage/structural effect of these copy number variants are likely explanations for the severe presentation in our patient.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2024 ","pages":"6319030"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10846923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genital Abnormalities and Growth Retardation as Early Signs of Dilated Cardiomyopathy with Ataxia Syndrome 生殖器畸形和生长发育迟缓是共济失调扩张型心肌病综合征的早期征兆

Case Reports in Genetics Pub Date : 2024-01-20 DOI: 10.1155/2024/8860889

K. Papadopoulou-Legbelou, Maria Ntoumpara, M. Kavga, Eleni P. Kotanidou, Ioannis Papoulidis, A. Galli-Tsinopoulou, Maria Fotoulaki

引用次数: 0

A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder 一种新型杂合子新MORC2缺义变异导致早发性严重神经发育障碍

Case Reports in Genetics Pub Date : 2024-01-02 DOI: 10.1155/2024/5906936

Daniel Arbide, N. Elkhateeb, Ewa Goljan, Carolina Perez Gonzalez, Anna Maw, Soo-Mi Park

{"title":"A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder","authors":"Daniel Arbide, N. Elkhateeb, Ewa Goljan, Carolina Perez Gonzalez, Anna Maw, Soo-Mi Park","doi":"10.1155/2024/5906936","DOIUrl":"https://doi.org/10.1155/2024/5906936","url":null,"abstract":"Microrchidia CW-type zinc finger protein 2 (MORC2) is an ATPase-containing nuclear protein which regulates transcription through chromatin remodelling and epigenetic silencing. MORC2 may have a role in the development of neurones, and dominant variants in this gene have recently been linked with disorders including Charcot-Marie-Tooth type 2Z disease, spinal muscular atrophy and, more recently, a neurodevelopmental syndrome consisting of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN), presenting with hypotonia, microcephaly, brain atrophy, intellectual disability, hearing loss, faltering growth, and craniofacial dysmorphism. Notably, variants in MORC2 have shown clinical features overlapping with those of Cockayne and Leigh syndromes. Here, we report a case of MORC2-related DIGFAN syndrome in a female infant caused by a novel heterozygous de novo variant. The condition was early onset and severe, further expanding the range of genotypes associated with this disorder. Clinical features included unilateral hearing loss, developmental delay and regression within the first year of life, microcephaly, severe feeding difficulties, and faltering growth, resulting in death at 13 months of age.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"120 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139391504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel SPAST Variant Associated with Isolated Spastic Paraplegia 与孤立性痉挛性截瘫相关的新型 SPAST 变异基因

Case Reports in Genetics Pub Date : 2023-12-31 DOI: 10.1155/2023/4553365

Helle Høyer, Ola Nakken, Trygve Holmøy

{"title":"A Novel SPAST Variant Associated with Isolated Spastic Paraplegia","authors":"Helle Høyer, Ola Nakken, Trygve Holmøy","doi":"10.1155/2023/4553365","DOIUrl":"https://doi.org/10.1155/2023/4553365","url":null,"abstract":"Genetic variants in SPAST are the most common cause of hereditary spastic paraplegia (HSP), entitled spastic paraplegia type 4 (SPG4). Inheritance is autosomal dominant, and age of onset can vary from childhood to adulthood. Pathogenic SPAST variants are often observed in isolated cases, likely due to reduced penetrance and clinical variability. We report an isolated case of SPG4 associated with a novel likely pathogenic variant in SPAST. A 38-year-old woman presented with an eight-year history of progressive difficulty walking. Neurological examination revealed spastic paraparesis in the absence of upper motor neuron dysfunction, sensory deficits, or intellectual disability. Magnetic resonance imaging (MRI) of the brain and spinal cord was normal. No family members had similar complaints. Genetic analysis revealed a novel heterozygous sequence variant in SPAST, c.1751A > G p.(Asp584Gly) (NM_014946.4). The affected amino acid is highly conserved among orthologue and paralogue species. Four other nucleotide substitutions predicted to affect the same amino acid, a “hot spot”, have been reported previously in adult-onset HSP. This report describes a novel SPAST variant in a female with HSP without a known family history of the disorder.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139134262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Diagnosis of Maternal 22q Duplication and Mosaic Deletion following Prenatal Cell-Free DNA Screening. 产前无细胞DNA筛查诊断母体22q重复和镶嵌缺失。

Case Reports in Genetics Pub Date : 2023-11-20 eCollection Date: 2023-01-01 DOI: 10.1155/2023/9127430

Melissa A Hicks, Emilie Lalonde, Jessica Zoladz, Bernard Gonik, Salah Ebrahim

{"title":"A Diagnosis of Maternal 22q Duplication and Mosaic Deletion following Prenatal Cell-Free DNA Screening.","authors":"Melissa A Hicks, Emilie Lalonde, Jessica Zoladz, Bernard Gonik, Salah Ebrahim","doi":"10.1155/2023/9127430","DOIUrl":"https://doi.org/10.1155/2023/9127430","url":null,"abstract":"Concurrent microduplication and microdeletion of the chromosome 22q11.2 region are a rarely reported phenomenon. We describe a case of germline 22q11.21 microduplication syndrome with concurrent mosaic 22q11.2 deletion in a pregnant patient, identified by chromosomal microarray and FISH after noninvasive prenatal genetic screening (cfDNA) results discordant with family history. The patient was referred to maternal-fetal medicine (MFM) at 14 weeks' gestation secondary to an SNP-based cfDNA result of a suspected maternal 22q11.2 deletion and a fetal risk of 1 in 2 for 22q11.2 deletion syndrome. The patient reported a similar cfDNA result in a previous pregnancy; however postnatal chromosomal microarray on that child identified an atypical 22q11.21 microduplication. We report the maternal chromosomal microarray findings of a germline 726 kb 22q11.21 duplication and a mosaic 1.33 Mb 22q11.2 deletion and highlight the copy number variant data generated by cfDNA in this unique case. This family adds to the limited literature of concurrent 22q11.2 microduplication and microdeletion carriers.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"9127430"},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Rare 46,X,t(Y;10)(q12;p14) Balanced Translocation in Non-Obstructive Azoospermic Patient with Elevated FSH and LH Levels 罕见的46,X,t(Y;10)(q12;p14)平衡易位在FSH和LH水平升高的非阻塞性无精子症患者中

Case Reports in Genetics Pub Date : 2023-11-13 DOI: 10.1155/2023/6722623

Kousar Jahan Syeeda Khursheed, Mohammed Rahman Kaleemullah, Annu Joseph, Mohammed Hasan Al Durazi, Moiz Bakhiet

{"title":"A Rare 46,X,t(Y;10)(q12;p14) Balanced Translocation in Non-Obstructive Azoospermic Patient with Elevated FSH and LH Levels","authors":"Kousar Jahan Syeeda Khursheed, Mohammed Rahman Kaleemullah, Annu Joseph, Mohammed Hasan Al Durazi, Moiz Bakhiet","doi":"10.1155/2023/6722623","DOIUrl":"https://doi.org/10.1155/2023/6722623","url":null,"abstract":"Structural chromosomal aberrations like translocations have been shown to cause spermatogenic failure. We report a rare 46,X,t(Y;10)(q12;p14) balanced translocation in an otherwise healthy non-obstructive azoospermic male with high follicle-stimulating hormone (26.65 IU/L) and high luteinizing hormone (13.58 IU/L). The patient was referred to us after clinical, hormonal, and histopathological investigations to identify chromosomal abnormalities by karyotyping and fluorescence in situ hybridization (FISH). Analysis of the banding pattern by karyotyping followed by FISH confirmed reciprocal translocation and identified the breakpoints at Yq heterochromatin (Yq12) and 10p14. Further molecular tests including AZF microdeletion assay were done, and the results, which showed no mutations in the analyzed genes, were provided by the referring doctor. Thus, our study points to the importance of conventional cytogenetic techniques in the preliminary evaluation of a genetic abnormality in cases of infertility and would help the patient make an informed decision before pursuing assisted reproductive technology.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"30 25","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0