American Journal of Medical Genetics Part A最新文献_第9页

Cerebellar Hypoplasia and Treatment Course of a Two-Month-Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature. 一名两个月大的 KCNQ2 癫痫脑病婴儿因新发型变异导致的小脑发育不全和治疗过程及文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-15 DOI: 10.1002/ajmg.a.63909

Dilek Cebeci, Busranur Cavdarli, Pinar Ozbudak, Ebru Arhan, Kivilcim Gucuyener, Ercan Demir

{"title":"Cerebellar Hypoplasia and Treatment Course of a Two-Month-Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature.","authors":"Dilek Cebeci, Busranur Cavdarli, Pinar Ozbudak, Ebru Arhan, Kivilcim Gucuyener, Ercan Demir","doi":"10.1002/ajmg.a.63909","DOIUrl":"https://doi.org/10.1002/ajmg.a.63909","url":null,"abstract":"In this paper, we report the treatment course, magnetic resonance imaging (MRI), and electroencephalography (EEG) findings of a two-month-old girl with KCNQ2 epileptic encephalopathy caused by a de novo variant. The patient started having seizures 2 days postnatally. Despite treatment with phenobarbital, phenytoin, levetiracetam, topiramate, clonazepam, vigabatrin, clobazam, and pyridoxine, she continued to have 10 or more seizures per day. EEG recordings showed multifocal epileptiform discharges with diffuse background slowing. MRI revealed left cerebellar hypoplasia. After lacosamide administration, the severity and frequency of seizures decreased by 80%. EEG recordings showed a significant improvement. A de novo heterozygous variant of c.1681C>A (p.Pro561Thr) in the KCNQ2 gene was detected. After carbamazepine add-on treatment, the patient achieved seizure-free status for about 2 years. This case demonstrates the efficacy of lacosamide against KCNQ2 epileptic encephalopathy. To our knowledge, this is the first report to document the association between cerebellar hypoplasia and KCNQ2 variants.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63909"},"PeriodicalIF":1.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455911","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

Advancing Equity in Rare Disease Research: Insights From the Undiagnosed Disease Network. 促进罕见病研究的公平性：未确诊疾病网络的洞察力。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-14 DOI: 10.1002/ajmg.a.63904

Nicholas A Borja, Rory J Tinker, Stephanie A Bivona, Carson A Smith, Theodore Krijnse Locker, Samuela Fernandes, John A Phillips, Justin Stoler, Herman Taylor, Stephan Zuchner, Mustafa Tekin

{"title":"Advancing Equity in Rare Disease Research: Insights From the Undiagnosed Disease Network.","authors":"Nicholas A Borja, Rory J Tinker, Stephanie A Bivona, Carson A Smith, Theodore Krijnse Locker, Samuela Fernandes, John A Phillips, Justin Stoler, Herman Taylor, Stephan Zuchner, Mustafa Tekin","doi":"10.1002/ajmg.a.63904","DOIUrl":"10.1002/ajmg.a.63904","url":null,"abstract":"Rare diseases affect 6%-8% of the population and present diagnostic challenges, particularly for historically marginalized ethnic and racial groups. The Undiagnosed Diseases Network (UDN) aims to enhance diagnosis rates and research participation among such minoritized groups. A retrospective review was conducted from 2015 to 2023, analyzing 2235 UDN participants to evaluate its progress toward this objective. Data on demographics, disease phenotypes, diagnostic outcomes, and socioeconomic factors were collected and statistical analyses assessed differences among ethnic and racial groups. This demonstrated that Hispanic and Black non-Hispanic groups were underrepresented, while White non-Hispanic participants were overrepresented in the UDN compared to the US population. Individuals whose primary language was not English were also significantly underrepresented. Diagnosis rates varied, with the highest rates among Asian non-Hispanic (39.5%) and Hispanic (35.3%) groups and the lowest rate in the White non-Hispanic group (26.8%) (p < 0.001). Binomial logistic regression found, however, that only participant age and disease phenotype predicted the likelihood of receiving a diagnosis (p < 0.001). Persistent ethnic and racial disparities in UDN participation appear to be associated with major differences in application rates. Under-enrollment of historically marginalized ethnic and racial groups may be due to economic hardships and language barriers. No differences in the diagnostic yield among ethnic and racial groups were observed after controlling for other factors. This work highlights the value of comprehensive genetic evaluations for addressing healthcare disparities and suggests priorities for advancing inclusion in rare disease research.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63904"},"PeriodicalIF":1.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455909","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

Clinical and Genetic Spectrum of Patients With Mitochondrial Disease in a Pediatric Egyptian Cohort: Novel Variants and Phenotypic Expansion. 埃及儿科队列中线粒体病患者的临床和遗传谱：新型变异和表型扩展。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-14 DOI: 10.1002/ajmg.a.63881

Hebatallah M Hassaan, Angela Pyle, Nihal Almenabawy, Fiona M Robertson, Nour Elkhateeb, Marian Y Girgis, Iman Gamal El Din Mahmoud, Fawzia Amer, Mona Samaha, Yara Shaheen, Walaa ElNaggar, Doaa Abdoh, Dina Ahmed Mehaney, Iman Ehsan Abdel Meguid, Robert W Taylor, Robert McFarland, Laila Selim

{"title":"Clinical and Genetic Spectrum of Patients With Mitochondrial Disease in a Pediatric Egyptian Cohort: Novel Variants and Phenotypic Expansion.","authors":"Hebatallah M Hassaan, Angela Pyle, Nihal Almenabawy, Fiona M Robertson, Nour Elkhateeb, Marian Y Girgis, Iman Gamal El Din Mahmoud, Fawzia Amer, Mona Samaha, Yara Shaheen, Walaa ElNaggar, Doaa Abdoh, Dina Ahmed Mehaney, Iman Ehsan Abdel Meguid, Robert W Taylor, Robert McFarland, Laila Selim","doi":"10.1002/ajmg.a.63881","DOIUrl":"https://doi.org/10.1002/ajmg.a.63881","url":null,"abstract":"Mitochondrial disorders exhibit clinical and genetic diversity. Nearly 400 distinct genes, located in both the mitochondrial and nuclear genomes, harbor pathogenic variants that can produce a broad spectrum of mitochondrial diseases. This work aims to explore the genetic etiology of a cohort of Egyptian pediatric patients who were clinically suspected of having a mitochondrial disorder. A total of 49 patients from 44 unrelated families were studied. Selection criteria included age below 18 years and meeting Morava criteria (a score ≥ 3). The mitochondrial disease criteria (MDC) have been developed to quantify the clinical picture and evaluate the probability of an underlying mitochondrial disorder Exome sequencing, including mitochondrial genome sequencing, was carried out for each participant. Causative variants likely responsible for the phenotypes were identified in 68% of the study population. The mitochondrial subgroup constituted 41% of the studied population with a median age of 4 years. No primary pathogenic variants in mitochondrial DNA were detected. Pathogenic or likely pathogenic variants in eight mitochondrial genes were identified in 78% of the mitochondrial cohort. Additionally, seven novel variants were identified. Nonmitochondrial diagnoses accounted for 27% of the study population. In 32% of cases, disease-causing variants were not identified. The current study underscores the diverse phenotypic and genetic landscape of mitochondrial disorders among Egyptian patients.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63881"},"PeriodicalIF":1.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455912","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

Table of Contents, Volume 194A, Number 11, November 2024 目录，第 194A 卷，第 11 号，2024 年 11 月

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-12 DOI: 10.1002/ajmg.a.63295

引用次数: 0

Genetic Factors Linked to Early Clinical Trial Termination 遗传因素与临床试验提前终止有关

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-12 DOI: 10.1002/ajmg.a.63292

引用次数: 0

Potential Therapy Corrects Calcium Signaling in Timothy Syndrome 纠正蒂莫西综合征钙信号的潜在疗法

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-12 DOI: 10.1002/ajmg.a.63293

引用次数: 0

Bullous Lung Disease in Turner Syndrome: An Underrecognized Comorbidity? 特纳综合征的牛肺病：未被充分认识的合并症？

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-11 DOI: 10.1002/ajmg.a.63908

Stevin Lu, Lois J Starr, Rachel A Taylor, Anji T Yetman

{"title":"Bullous Lung Disease in Turner Syndrome: An Underrecognized Comorbidity?","authors":"Stevin Lu, Lois J Starr, Rachel A Taylor, Anji T Yetman","doi":"10.1002/ajmg.a.63908","DOIUrl":"10.1002/ajmg.a.63908","url":null,"abstract":"Congenital pulmonary anomalies in Turner syndrome (TS) are rarely reported. Herein, we describe a female with TS who presented with emphysema in infancy and developed pulmonary hypertension in adulthood. A 4-month-old patient presented with recurrent emesis and failure to thrive. Diagnostic testing indicated cardiomegaly and echocardiogram revealed abnormalities including left aortic arch with aberrant right subclavian artery, aortic coarctation, and left ventricular (LV) dysfunction. At 19-months, she underwent surgical intervention through a lateral thoracotomy which exposed numerous small air-filled blebs over the left lung. She had persistent LV dysfunction postoperatively. At 12-years-old, genetic testing revealed 45,X/46,Xidic(Y)(q11.22) and she subsequently received routine treatment for Turner syndrome. At 23-years-old, this patient presented to the emergency department with dyspnea, worsening cough, and edema. Echocardiogram demonstrated a reduced LVEF, aortic valve insufficiency, and pulmonary artery (PA) hypertension. CT chest showed multiple apical blebs and cardiac catheterization demonstrated pulmonary hypertension. She was treated with intravenous diuresis and cessation of Humira, which normalized LVEF and reduced PA pressure. Repeat cardiac catheterization 6 months later indicated elevated LVEDP, pulmonary vascular resistance, and mean PA pressures. Altered lymphatic drainage in utero of patients with TS may lead to emphysematous changes in the lungs. These changes may not raise concern in infancy but can possibly contribute to cardiopulmonary pathology in the future. We recommend ongoing routine care to monitor for acquired cardiopulmonary co-morbidities. Bullous lung disease may occur due to altered lymphatic drainage in patients with TS and may be a risk factor for developing or contributing to pulmonary hypertension.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63908"},"PeriodicalIF":1.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399112","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

Managing CDH1 Cancer Risks in a Child: Complex Decision Making in a Family With Hereditary Diffuse Gastric Cancer. 管理儿童 CDH1 癌症风险：遗传性弥漫性胃癌家庭的复杂决策。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-11 DOI: 10.1002/ajmg.a.63897

Nihat Bugra Agaoglu, Ozden Hatirnaz Ng, Itir Ebru Zemheri, Busra Unal, Nelgin Gerenli, Ilkay Tosun, Hulya Yazıcı, Ugur Ozbek, Junne Kamihara, Huma Q Rana

引用次数: 0

A Distinctive Type of Mosaic Variegated Aneuploidy: Case Report and Review of the Literature. 一种独特的马赛克变异型非整倍体：病例报告和文献综述。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-11 DOI: 10.1002/ajmg.a.63901

Annalisa Frattini, Giovanni Micheloni, Antonio Musio, Marika Bini Antunes, José Barbot, Emília Costa, Patricia Seabra, Rossana Righi, Francesco Orsini, Giuseppe Montalbano, Francesco Acquati, Giovanni Porta, Francesco Pasquali, Roberto Valli

{"title":"A Distinctive Type of Mosaic Variegated Aneuploidy: Case Report and Review of the Literature.","authors":"Annalisa Frattini, Giovanni Micheloni, Antonio Musio, Marika Bini Antunes, José Barbot, Emília Costa, Patricia Seabra, Rossana Righi, Francesco Orsini, Giuseppe Montalbano, Francesco Acquati, Giovanni Porta, Francesco Pasquali, Roberto Valli","doi":"10.1002/ajmg.a.63901","DOIUrl":"https://doi.org/10.1002/ajmg.a.63901","url":null,"abstract":"Mosaic variegated aneuploidy (MVA) is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies, and most patients present with intrauterine growth delay, microcephaly, and a broad spectrum of congenital abnormalities. We report a patient with a distinctive type of MVA discovered in bone marrow (BM) when she was 3-month-old due to neutropenia and hypocellular bone marrow. She was followed up for more than 20 years, and different trisomic cells were repeatedly discovered in different tissues, whereas her clinical picture has never been severe. The main sign remained intermittent neutropenia, not cyclic and often not too severe, occasionally with anemia and thrombocytopenia. Retromicrognathia was the only dysmorphic sign. Unlike other patients with MVA, the trisomies in all tissues involved almost invariably chromosomes 18 and 19. Therefore, the peculiarities of our patient were the clinical and the atypical cytogenetic pictures. Nevertheless, we looked for mutations in the seven causative genes of the known types of MVA, but the results were negative. Then, we analyzed the entire exome to find out other possible causing mutations, but also this attempt failed to discover a possible cause of this distinctive form of MVA.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63901"},"PeriodicalIF":1.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399111","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

Non-Hotspot PIK3CA Variants Have Higher Variant Allele Frequency and are More Common in Syndromic Vascular Malformations. 非热点 PIK3CA 变异具有更高的变异等位基因频率，在综合征血管畸形中更为常见。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-07 DOI: 10.1002/ajmg.a.63883

Themis-Areti A Andreoti, Massimo Maiolo, Aleksandra Tuleja, Yvonne Döring, André Schaller, Erik Vassella, Laurence M Boon, Iris Baumgartner, Sarah M Bernhard, Christiane Zweier, Miikka Vikkula, Jochen Rössler

{"title":"Non-Hotspot PIK3CA Variants Have Higher Variant Allele Frequency and are More Common in Syndromic Vascular Malformations.","authors":"Themis-Areti A Andreoti, Massimo Maiolo, Aleksandra Tuleja, Yvonne Döring, André Schaller, Erik Vassella, Laurence M Boon, Iris Baumgartner, Sarah M Bernhard, Christiane Zweier, Miikka Vikkula, Jochen Rössler","doi":"10.1002/ajmg.a.63883","DOIUrl":"https://doi.org/10.1002/ajmg.a.63883","url":null,"abstract":"PIK3CA variants are known to cause vascular malformations. We were interested in studying the phenotypic spectrum, the location within the PIK3CA gene, and the variant allele frequency (VAF) of somatic PI3KCA variants in vascular malformations. Clinical data of consecutive patients with extracranial/extraspinal vascular malformations were collected in the context of the VASCOM cohort (2008-2022, n = 558). Starting October 2020, biopsy samples were tested with the TSO500 gene panel (Illumina). All consenting patients with PIK3CA variants were included in this study. Eighty-nine patients had available genetic results by June 2022. PIK3CA variants (n = 25) were found in 16 simple/combined (nonsyndromic) vascular malformations and in nine vascular malformations associated with other anomalies (syndromic). Four hotspot variants in exons 9 and 20 (c.1624G>A, c.1633G>A, c.3140A>G, c.3140A>T) were identified in 16/25 patients (VAF 0.9%-9.7%). Six non-hotspot variants (c.328_330del, c.323_337del, c.353G>A, c.1258T>C, c.3132T>A, c.3195_3203delinsT) were detected in nine patients (VAF 3.6%-31.7%). Non-hotspot variants were more frequent in syndromic than nonsyndromic vascular malformations (p = 0.0034) and exhibited a higher VAF than hotspot variants (p = 0.0253). Our study contributes to the growing body of knowledge of the genetic background in vascular malformations. Further studies will enrich the ever-growing list of pathogenic PIK3CA variants associated with vascular malformations.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63883"},"PeriodicalIF":1.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387250","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