American Journal of Medical Genetics Part A最新文献_第10页

De Novo Variants in LRRC8C Linked to Rare Disorder 与罕见疾病相关的LRRC8C从头变异

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-06 DOI: 10.1002/ajmg.a.63740

引用次数: 0

Table of Contents, Volume 197A, Number 4, April 2025 目录，197A卷，第4号，2025年4月

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-06 DOI: 10.1002/ajmg.a.63743

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Expanding the Genetic Spectrum of PPM1K-Related Maple Syrup Urine Disease: A Novel Mutation. 扩大ppm1k相关的枫糖浆尿病的遗传谱：一个新的突变。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-06 DOI: 10.1002/ajmg.a.64037

Mustafa Kılıç, Esra Sayar, Suzan İcil, Sevgi Doğan, Gizem Gökçe-Altaş, Can Koşukcu, Abdüllatif Bakır, Abdullah Sezer

{"title":"Expanding the Genetic Spectrum of PPM1K-Related Maple Syrup Urine Disease: A Novel Mutation.","authors":"Mustafa Kılıç, Esra Sayar, Suzan İcil, Sevgi Doğan, Gizem Gökçe-Altaş, Can Koşukcu, Abdüllatif Bakır, Abdullah Sezer","doi":"10.1002/ajmg.a.64037","DOIUrl":"https://doi.org/10.1002/ajmg.a.64037","url":null,"abstract":"Maple syrup urine disease (MSUD) is a rare inborn error of metabolism caused by impaired catabolism of branched-chain amino acids (BCAAs). The genes BCKDHA, BCKDHB, DBT, and DLD encode the subunits of the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which is essential for BCAA metabolism. Catalytic subunits are BCKDHA, BCKDHB, DBT, and DLD, whereas the regulator subunits are PPM1K and BCKDK. PPM1K plays a critical role by dephosphorylating and activating this enzyme complex. Pathogenic variants in the PPM1K gene cause an extremely rare, mild form of MSUD. Here, we report an 8-year-old male patient with a mild form of MSUD putatively caused by a novel homozygous variant in PPM1K. The patient presented with mild dysmorphic features, delayed speech, relative microcephaly, and overweight, all considered familial phenotypic traits. Laboratory findings revealed mildly elevated plasma branched-chain amino acids, mild lactic acidemia, and a slight increase in urinary keto acids. Exome sequencing identified a novel homozygous missense variant, c.925A>G p.(Ile309Val), in the PPM1K gene. This case represents the third reported patient with a mild form of MSUD associated with the first reported missense variant in the PPM1K gene in the literature, further expanding the clinical and genetic spectrum of PPM1K-related disorders.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64037"},"PeriodicalIF":1.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565770","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}

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First Report of Phosphoglycerate Kinase Deficiency in a Dinè Child With Review of Current Literature. 首次报道在Dinè儿童磷酸甘油酸激酶缺乏与当前文献回顾。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-03 DOI: 10.1002/ajmg.a.64034

Ariel Hierholzer, Jillian Mador, Rachna Guntu, Kristian Schafernak, Theresa A Grebe

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New Genitourinary Findings in CTNND1 Blepharocheilodontic Syndrome. CTNND1睑缘牙综合征的泌尿生殖系统新发现。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-03 DOI: 10.1002/ajmg.a.64033

Lily Loughman, Naeem Samnakay, Geoffrey C Lam, Sarah-Jane Pantaleo, Ain Roesley, Benjamin Kamien

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Detecting the Difficult: An Intronic NPC1 Variant Hiding in Plain Sight. 检测困难：隐藏在视线中的内含子NPC1变体。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-03-03 DOI: 10.1002/ajmg.a.64012

Caroline Gully Brown, Matthew Bower, Matthew Schomaker, Jessica Goldstein, Jeanine Jarnes, Chester B Whitley, Nishitha R Pillai

{"title":"Detecting the Difficult: An Intronic NPC1 Variant Hiding in Plain Sight.","authors":"Caroline Gully Brown, Matthew Bower, Matthew Schomaker, Jessica Goldstein, Jeanine Jarnes, Chester B Whitley, Nishitha R Pillai","doi":"10.1002/ajmg.a.64012","DOIUrl":"https://doi.org/10.1002/ajmg.a.64012","url":null,"abstract":"An illustration of the importance of manual data review for identifying rare intronic variants adjacent to homopolymers is presented here. A 14-year-old male with Niemann-Pick Type C disease confirmed biochemically was only found to have a heterozygous pathogenic variant by molecular analysis. A manual review of the Next Generation Sequencing (NGS) data identified a c.709C>T; p.Pro237Ser variant, which was likely not reported initially because it is consistently classified as benign or likely benign. A rare association of the c.709C>T variant with a second intronic NPC1 variant (c.1947 + 5G>C) leading to the use of a cryptic splice donor site has been reported before. Further evaluation with Sanger sequencing detected the c.1947 + 5G>C variant as the second causative variant in this patient. Detection of a second allelic change in autosomal recessive inborn errors of metabolism and other genetic disorders is vital in establishing a diagnosis, initiating new therapies, and testing at risk family members. The case presented here illustrates a rare intronic splice site NPC1 variant that may not be readily detected by current short-read NGS technologies due to the downstream homopolymers and should be evaluated regularly, especially in the presence of another heterozygous variant.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64012"},"PeriodicalIF":1.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539901","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

Natural History and Diagnostic Findings in an Adult Man Diagnosed With Attenuated Krabbe Disease. 一名被诊断患有减弱型克拉伯病的成人的自然史和诊断结果。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-02-28 DOI: 10.1002/ajmg.a.64031

Eamon P McCarron, Andrew Oldham, Amit Herwadkar, Sarah Jenkinson, Christopher Campbell, Kate Neal, Heather J Church, James A Cooper, Karolina M Stepien

{"title":"Natural History and Diagnostic Findings in an Adult Man Diagnosed With Attenuated Krabbe Disease.","authors":"Eamon P McCarron, Andrew Oldham, Amit Herwadkar, Sarah Jenkinson, Christopher Campbell, Kate Neal, Heather J Church, James A Cooper, Karolina M Stepien","doi":"10.1002/ajmg.a.64031","DOIUrl":"https://doi.org/10.1002/ajmg.a.64031","url":null,"abstract":"Krabbe disease (KD), or globoid cell leukodystrophy, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in galactocerebrosidase (GALC), leading to psychosine (galactosylsphingosine) accumulation and myelin damage. The natural history of the attenuated form is poorly understood, but it typically presents with spastic paraparesis, progressing more slowly than the early-onset or infantile variant. Diagnosis relies on a high index of clinical suspicion, imaging studies, biochemistry, and molecular analysis. Magnetic resonance imaging (MRI) demonstrates characteristic corticospinal tract involvement, while cerebrospinal fluid analysis can reveal elevated protein levels. We present a case of late-onset KD in a 55-year-old male with a novel pathogenic GALC variant, aiming to highlight the features and investigation findings that should prompt consideration of the diagnosis. In addition, we describe the course of illness, emphasizing the importance of multi-disciplinary team (MDT) input in patient care and the role of novel blood-based and imaging biomarkers.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e64031"},"PeriodicalIF":1.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522340","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

Phenotypic Characteristics of a Patient Cohort With Recessive Dystrophic Epidermolysis Bullosa and the Pathogenic Variant c.7485+5G>A in Intron 98 of COL7A1. 隐性营养不良大疱性表皮松解症患者队列与COL7A1基因98内含子c.7485+5G> a致病变异的表型特征

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-02-27 DOI: 10.1002/ajmg.a.64032

Micah G Pascual, Hannah C Cox, Austin Larson, Anna L Bruckner

引用次数: 0

Myotonic Dystrophy and Stress Induced Cardiomyopathy: A Case Series 强直性肌营养不良和应激性心肌病：一个病例系列。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-02-25 DOI: 10.1002/ajmg.a.64027

Anindita Chanda, Damla C. Gonullu-Rotman, Mohammed Elsadany, Stephanie Saucier, Irina Sobol, Shudhanshu Alishetti, Ningxin Wan, Sean R. McMahon, Omar A. Abdul-Rahman

{"title":"Myotonic Dystrophy and Stress Induced Cardiomyopathy: A Case Series","authors":"Anindita Chanda, Damla C. Gonullu-Rotman, Mohammed Elsadany, Stephanie Saucier, Irina Sobol, Shudhanshu Alishetti, Ningxin Wan, Sean R. McMahon, Omar A. Abdul-Rahman","doi":"10.1002/ajmg.a.64027","DOIUrl":"10.1002/ajmg.a.64027","url":null,"abstract":"<div>\u0000 \u0000 Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder with a broad spectrum of systemic manifestations, including cardiac abnormalities. Takotsubo cardiomyopathy, a form of stress-induced transient heart failure, is not typically associated with DM1, and its occurrence in this patient population remains poorly characterized. This case series aims to describe two instances of Takotsubo cardiomyopathy in patients with DM1, highlighting potential links between the neuromuscular and cardiac pathophysiology of DM1 and stress-induced cardiomyopathy. We reviewed the clinical presentation, diagnostic findings, and outcomes of two patients with genetically confirmed DM1 who developed Takotsubo cardiomyopathy. Data were collected from medical records, including electrocardiograms, echocardiograms, cardiac biomarkers, and imaging studies. A review of the literature was conducted to contextualize the findings. The two patients presented in this case series exhibited distinct triggers and clinical presentations. The first patient, a 39-year-old woman, developed chest pain following intractable nausea and vomiting, while the second patient, a 62-year-old woman, experienced palpitations after the emotional stress of her 28-year-old daughter's passing. Despite these differing triggers, both cases showed imaging findings characteristic of Takotsubo cardiomyopathy, including left ventricular apical ballooning and reduced ejection fraction. Both patients were diagnosed with DM1, and their cardiac functions fully recovered within weeks. This case series highlights the importance of recognizing Takotsubo cardiomyopathy as a potential cardiac complication in patients with DM1. Shared neuromuscular and cardiac pathophysiology between DM1 and Takotsubo cardiomyopathy warrants further investigation to elucidate underlying mechanisms and guide management strategies.\u0000 </div>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"197 6","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497772","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}

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Immediate Therapeutic Response to Vigabatrin in Lissencephaly-Related Epileptic Spasms due to TUBA1A R402H Variant. TUBA1A R402H变异引起的缺脑症相关癫痫痉挛，Vigabatrin即刻治疗反应

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2025-02-25 DOI: 10.1002/ajmg.a.64030

Toru Nagata, Takashi Shibata, Hiroki Tsuchiya, Mari Akiyama, Mitsuhiro Kato, Tomoyuki Akiyama, Toshiki Takenouchi

引用次数: 0