American Journal of Medical Genetics Part A最新文献_第5页

Sodium Oxybate-Treated Familial Myoclonus-Dystonia Syndrome Due to Novel SGCE Variant. 氧酸钠治疗由新型SGCE变异引起的家族性肌阵挛-肌张力障碍综合征。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-20 DOI: 10.1002/ajmg.a.63964

Malak Ali Alghamdi, Muddathir H Hamad, Isra Alghamdi, Ghiada Alghamdi, Muneera Al-Jelaify, Sohaila Alshimemeri, Hebattalah Hamed, Nouran Adly, Mustafa A Salih, Naif A Almontashiri, Fahad A Bashiri

{"title":"Sodium Oxybate-Treated Familial Myoclonus-Dystonia Syndrome Due to Novel SGCE Variant.","authors":"Malak Ali Alghamdi, Muddathir H Hamad, Isra Alghamdi, Ghiada Alghamdi, Muneera Al-Jelaify, Sohaila Alshimemeri, Hebattalah Hamed, Nouran Adly, Mustafa A Salih, Naif A Almontashiri, Fahad A Bashiri","doi":"10.1002/ajmg.a.63964","DOIUrl":"https://doi.org/10.1002/ajmg.a.63964","url":null,"abstract":"Myoclonus-dystonia syndrome (MDS, OMIM #159900) is an autosomal-dominant movement disorder caused by heterozygous variants in the epsilon sarcoglycan gene (SGCE) and characterized by a combination of myoclonic jerks, dystonia, and psychiatric comorbidities. Patients with MDS have a normal life expectancy with markedly reduced quality of life. Here, we report four family members diagnosed with MDS of variable severity due to a novel heterozygous splicing variant in SGCE (c.341-2A>G), including a 13-year-old female who presented with disabling dystonic spasms, myoclonic jerks, and psychiatric symptoms. She had shown little or no response to several conventional MDS treatments. However, disabling axial dystonia was significantly improved by sodium oxybate (1 g, twice daily). Although there was less effect on myoclonus, sodium oxybate treatment significantly improved the overall quality of life at the 3-years follow-up. Clinical trials are warranted to assess the clinical efficacy and safety of sodium oxybate for MDS-associated dystonia.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63964"},"PeriodicalIF":1.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expansion of the Phenotype of You-Hoover-Fong Syndrome and Possible Increased Risk of Cancer. 尤-胡佛-方综合征表型的扩展和可能增加的癌症风险。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-20 DOI: 10.1002/ajmg.a.63966

Alessandro De Falco, Fabiola De Gregorio, Massimo Eraldo Abate, Chiara Paolella, Vincenzo Nigro, Iris Scala, Nicola Brunetti-Pierri

引用次数: 0

Recurrent FLNA p.Gly1554Arg Variant Associated With Familial Ebstein Anomaly and Joint Stiffness. 复发性FLNA p.Gly1554Arg变异与家族性Ebstein异常和关节僵硬相关。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-20 DOI: 10.1002/ajmg.a.63973

Yukiko Kuroda, Koki Nagai, Yasuhiro Kawai, Takuya Wakamiya, Takuya Naruto, Kenji Kurosawa

引用次数: 0

A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis. 纯合子MYH1变异是常染色体隐性分离的复发性横纹肌溶解的基础。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-17 DOI: 10.1002/ajmg.a.63952

Eyyup Uctepe, Hanifenur Mancılar, Fatma Nisa Esen, Gokcen Gundogdu Unverengil, Barbara Vona, Ahmet Yesilyurt

{"title":"A Homozygous MYH1 Variant Underlies Autosomal Recessive Isolated Recurrent Rhabdomyolysis.","authors":"Eyyup Uctepe, Hanifenur Mancılar, Fatma Nisa Esen, Gokcen Gundogdu Unverengil, Barbara Vona, Ahmet Yesilyurt","doi":"10.1002/ajmg.a.63952","DOIUrl":"https://doi.org/10.1002/ajmg.a.63952","url":null,"abstract":"Rhabdomyolysis is a severe condition involving the breakdown of skeletal muscle fibers, leading to the release of muscle components into the bloodstream, which can lead to potential complications such as acute kidney injury and electrolyte imbalances. The etiology of rhabdomyolysis is multifactorial, encompassing traumatic, exertional, metabolic, infectious, toxic, and genetic causes. Genetic causes, including variants in LPIN1, RYR1, and CACNA1S, are increasingly recognized as significant contributors to recurrent rhabdomyolysis. MYH1 has recently been identified as a candidate gene for recurrent rhabdomyolysis with limited evidence originating from a single patient. In this report, we describe a 35-year-old male, born to consanguineous parents, who presented with recurrent rhabdomyolysis attacks, beginning at age 28, characterized by muscle pain, weakness, and episodes of acute kidney injury requiring dialysis. During attacks, the patient exhibited remarkably elevated markers of muscle breakdown and mildly elevated creatine kinase levels between episodes. A muscle biopsy revealed non-specific myopathic changes. Exome sequencing analysis was carried out and revealed a novel homozygous variant (NM_005963.4: c.1825G>A [p.Val609Met]) in MYH1 segregating in a manner compatible with an autosomal recessive pattern. In summary, this case provides confirmatory support for the role of pathogenic MYH1 variants in the pathogenesis of recurrent rhabdomyolysis and emphasizes the importance of comprehensive genetic testing in patients with unexplained recurrent episodes of muscle breakdown. Further cases are necessary to fully elucidate the genotypic and phenotypic spectrum of MYH1-related muscle disorders.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63952"},"PeriodicalIF":1.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebrospinal Fluid and Serum Neuron-Specific Enolase in Niemann-Pick Disease Type C1. Niemann-Pick病C1型的脑脊液和血清神经元特异性烯醇化酶

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-17 DOI: 10.1002/ajmg.a.63970

Cameron J Padilla, Derek M Alexander, Desiree A Labor, Orsolya K Albert, Kendall P Robbins, Elizabeth Berry-Kravis, Forbes D Porter

{"title":"Cerebrospinal Fluid and Serum Neuron-Specific Enolase in Niemann-Pick Disease Type C1.","authors":"Cameron J Padilla, Derek M Alexander, Desiree A Labor, Orsolya K Albert, Kendall P Robbins, Elizabeth Berry-Kravis, Forbes D Porter","doi":"10.1002/ajmg.a.63970","DOIUrl":"https://doi.org/10.1002/ajmg.a.63970","url":null,"abstract":"Niemann-Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron-specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum and cerebrospinal fluid (CSF) NSE measurements. A total of 34 individuals with NPC1 were included in this analysis. Overall, 10 participants were used to compare concurrent samples of CSF and serum NSE. NSE levels were correlated with indexes of disease severity (Annual Severity Increment Score [ASIS] and age of neurological onset) and disease burden (NPC Neurological Severity Score [NSS]). NSE was elevated in CSF, but paired CSF/serum samples were not correlated (rs = -0.16, p = 0.64). Additionally, no significant correlations were observed between serum NSE levels and clinical measures of either disease burden or severity. CSF NSE values showed a significant positive association with the ASIS (rs = 0.37, p = 0.0291) but no association with age of neurological onset or NPC NSSs. Longitudinal analysis of nine participants showed a significant (p = 0.0317) decrease in CSF NSE levels after initiation of intrathecal 2-hydroxypropyl-β-cyclodextrin (IT HPβCD) therapy. This study suggests that CSF NSE may have some utility as a biomarker in NPC1 therapeutic trials.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63970"},"PeriodicalIF":1.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Insights Into Epidermolysis Bullosa: Identification of Novel Variants in Tunisian Patients. 大疱性表皮松解症的遗传学研究：突尼斯患者新变异的鉴定。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-17 DOI: 10.1002/ajmg.a.63967

Haifa El Mabrouk, Houcemeddine Othman, Lobna Boussofarra, Moez Gribaa, Ali Saad, Mohamed Denguezli, Cristina Has, Dorra H'mida

{"title":"Genetic Insights Into Epidermolysis Bullosa: Identification of Novel Variants in Tunisian Patients.","authors":"Haifa El Mabrouk, Houcemeddine Othman, Lobna Boussofarra, Moez Gribaa, Ali Saad, Mohamed Denguezli, Cristina Has, Dorra H'mida","doi":"10.1002/ajmg.a.63967","DOIUrl":"https://doi.org/10.1002/ajmg.a.63967","url":null,"abstract":"Epidermolysis Bullosa (EB) is a group of genetic skin disorders characterized by extreme skin fragility and blistering. In North African countries, including Tunisia, complex genetic and phenotypic diversity is entangled with a scarcity of scientific research on EB. This lack of knowledge presents a distinct challenge in terms of diagnostic accuracy and patient care. Our study cohort includes 10 Tunisian patients with EB whose genetic profiles were investigated by exome sequencing. In silico analysis was conducted to determine the functional impact of three novel variants. We revealed ten genetic variants, including three novel ones within the COL7A1 and DST genes. The in silico analysis shed light on the potential structural and functional implications of these novel variants. By establishing the correlation between clinical features and genetic alterations, we have expanded the existing database of disease-causing variants associated with EB in Northern Africa. Our study fills a critical knowledge gap in the North African context, where the scarcity of clinical database and genetic testing in addition to the genetic diversity necessitates comprehensive research. Our findings have the potential to improve diagnosis and management strategies for EB patients in low and middle-income countries across the region, especially through the integration of exome sequencing and in silico analysis.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63967"},"PeriodicalIF":1.7,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

COL4A2-Related Disorder Presenting in Adulthood With Rhabdomyolysis. 成年横纹肌溶解患者col4a2相关疾病

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-16 DOI: 10.1002/ajmg.a.63965

Bukola A Olarewaju, Judy Tejon, Shaymaa Shurrab, Alicia Chen, Fadi Shamoun, Benn E Smith, Mayowa A Osundiji

{"title":"COL4A2-Related Disorder Presenting in Adulthood With Rhabdomyolysis.","authors":"Bukola A Olarewaju, Judy Tejon, Shaymaa Shurrab, Alicia Chen, Fadi Shamoun, Benn E Smith, Mayowa A Osundiji","doi":"10.1002/ajmg.a.63965","DOIUrl":"https://doi.org/10.1002/ajmg.a.63965","url":null,"abstract":"The alpha 1 and 2 chains of type IV collagen, encoded by the COL4A1 (MIM 120130) and COL4A2 (MIM 120090) respectively, play essential roles in the vascular basement membranes. Pathogenic variants in COL4A1/ COL4A2 are associated with autosomal dominant cerebral angiopathies. The clinical manifestations of COL4A1/COL4A2-related disorders include: aneurysms, intracerebral hemorrhage, polymicrogyria, porencephaly, heterotopia, periventricular leukomalacia, epilepsy, and neurodevelopmental disorders. COL4A1 pathogenic variants that are in exons 24 and 25 have been associated with hereditary angiopathy, nephropathy, aneurysms, and cramps. The multisystemic phenotypes of COL4A1/COL4A2-related disorders are increasingly being studied. Animal models have suggested that COL4A2-related disorders may also manifest with a variable combination of multisystemic abnormalities affecting the eyes, muscles, and kidneys. Okano and colleagues recently reported a case of recurrent episodes of rhabdomyolysis in a 2-year-old with COL4A1-related disorder raising fundamental questions on mechanisms of COL4A1/COL4A2 variants in muscle homeostasis. To date, rhabdomyolysis has not been associated with COL4A2-related disorder in humans. Rhabdomyolysis is a medical emergency, where there is elevated creatine kinase (CK) level in the blood and increased excretion of myoglobin in urine, due to skeletal muscle damage and release of intracytoplasmic proteins into systemic circulation. Rhabdomyolysis is a serious medical condition. It require intensive care management due to an increased risk of some life-threatening complications [including disseminated intravascular coagulation, renal failure, and severe hyperkalemia]. Herein, we report a case of rhabdomyolysis in an adult with COL4A2-related structural brain malformations (including polymicrogyria and heterotopia).","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63965"},"PeriodicalIF":1.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Community-Sourced Reporting of Mortalities in Angelman Syndrome (1979-2022). 天使综合征死亡率的社区来源报告（1979-2022）。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-16 DOI: 10.1002/ajmg.a.63961

Adriana T Gomes, Amanda Moore, Meagan Cross, Cristy Hardesty, Kelly David, Maria Galan Sampedro, Sophie Dube, Sharon Weil-Chalker, Adela Gentil Montepagano, Ursula Christel, Rachel Martin, Anne Wheeler, Wen-Hann Tan, Lynne M Bird, Terry Jo Bichell

{"title":"Community-Sourced Reporting of Mortalities in Angelman Syndrome (1979-2022).","authors":"Adriana T Gomes, Amanda Moore, Meagan Cross, Cristy Hardesty, Kelly David, Maria Galan Sampedro, Sophie Dube, Sharon Weil-Chalker, Adela Gentil Montepagano, Ursula Christel, Rachel Martin, Anne Wheeler, Wen-Hann Tan, Lynne M Bird, Terry Jo Bichell","doi":"10.1002/ajmg.a.63961","DOIUrl":"10.1002/ajmg.a.63961","url":null,"abstract":"Angelman syndrome (AS) is a severe genetic neurodevelopmental disorder with an estimated prevalence of 1:20,000. Life expectancy appears to be normal, however, data regarding lifespan in AS are scarce. Until 2018, there was no unique diagnosis code for AS, thus true incidence, prevalence, mortality and morbidity rates are unknown. A social media effort was launched by caregivers of people with AS to gather community-sourced data to understand AS mortality risks. Information on 220 deaths was verified with obituaries and public postings. Respiratory illness was the primary cause of death among people with AS overall, followed by accidents and seizures. Surprisingly, sudden unexpected death in sleep (SUDS) was the fourth most common cause, which has not been reported previously. Approximately 91% of people with AS have epilepsy, thus some SUDS cases may represent sudden unexpected deaths in epilepsy (SUDEP). Causes of death vary by age, and differ from the general population. Though there are obvious limitations to data collected through social media, grass roots science is a starting point to amass preliminary data and inform future epidemiological research on AS.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63961"},"PeriodicalIF":1.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins. 单卵双胞胎和异卵双胞胎的转录组和代谢组分析

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-16 DOI: 10.1002/ajmg.a.63971

Nikki Hubers, Gabin Drouard, Rick Jansen, René Pool, Jouke Jan Hottenga, Miina Ollikainen, Xiaoling Wang, Gonneke Willemsen, Jaakko Kaprio, Dorret I Boomsma, Jenny van Dongen

{"title":"Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.","authors":"Nikki Hubers, Gabin Drouard, Rick Jansen, René Pool, Jouke Jan Hottenga, Miina Ollikainen, Xiaoling Wang, Gonneke Willemsen, Jaakko Kaprio, Dorret I Boomsma, Jenny van Dongen","doi":"10.1002/ajmg.a.63971","DOIUrl":"https://doi.org/10.1002/ajmg.a.63971","url":null,"abstract":"Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins. We analyzed 42,663 RNA transcripts in 1453 MZ twins and 1294 DZ twins from the Netherlands Twin Register (NTR), followed by sex-stratified analyses. The top 5% transcripts with lowest p-values were analyzed for replication in 217 MZ and 158 DZ twins from the older Finnish Twin cohort (FTC). In the NTR, one transcript (PURG) was significantly differentially expressed between MZ and DZ twins; but this did not replicate in FTC. Pathway analyses highlighted the WNT-pathway, previously associated with MZ twinning, and the TGF-B and SMAD pathway, previously associated with DZ twinning. Meta-analysis of 169 serum metabolites in 2797 MZ and 2040 DZ twins from the NTR, FTC and FinnTwin12, showed no metabolomic differences. Overall, we did not find replicable transcript-level expression differences in blood between MZ and DZ twins, but highlighted the TGF-B/SMAD pathway as a potential transcriptional biomarker for DZ twinning.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63971"},"PeriodicalIF":1.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeat Expansion Disorders Likely Underdiagnosed 重复扩张障碍可能未被诊断。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-12-12 DOI: 10.1002/ajmg.a.63728

引用次数: 0