American Journal of Medical Genetics Part A最新文献_第4页

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":null,"pages":null},"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

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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":null,"pages":null},"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}

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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

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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":null,"pages":null},"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}

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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":null,"pages":null},"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}

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Neurodevelopment in Young Children With Sex Chromosome Trisomies Diagnosed Before Birth: A Cluster Analysis Study. 出生前诊断出性染色体三体的幼儿的神经发育：聚类分析研究

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.63895

Laura Zampini, Alessandra Lorini, Paola Zanchi, Nicoletta Scionti, Gaia Silibello, Francesca Dall'Ara, Paola Francesca Ajmone, Federico Monti, Maria Antonella Costantino, Paola Giovanna Vizziello

{"title":"Neurodevelopment in Young Children With Sex Chromosome Trisomies Diagnosed Before Birth: A Cluster Analysis Study.","authors":"Laura Zampini, Alessandra Lorini, Paola Zanchi, Nicoletta Scionti, Gaia Silibello, Francesca Dall'Ara, Paola Francesca Ajmone, Federico Monti, Maria Antonella Costantino, Paola Giovanna Vizziello","doi":"10.1002/ajmg.a.63895","DOIUrl":"https://doi.org/10.1002/ajmg.a.63895","url":null,"abstract":"Many studies have investigated the neuropsychological profile of individuals with sex chromosome trisomies (SCTs) and have identified some fragilities in language development within a wide individual variability. However, only a few studies have focused on children in the second year of life (12-24 months), a crucial stage for neurodevelopment. The present study aimed to identify and describe neurodevelopmental patterns in young children with SCTs. Seventy children with SCTs, ranging in age from 14 to 29 months, were administered the Griffiths Mental Development Scales, and their different neurodevelopmental profiles were identified using cluster analysis. Two-step cluster analysis highlighted two profiles of children equally distributed between groups. The two clusters showed a similar pattern but different levels of functioning, with children in Cluster 1 showing a lower performance in all the areas considered than children in Cluster 2. However, in both clusters, all the mean scores were in the normative range, with a significant gap in the linguistic area. Identifying the subgroups of young children with SCTs at higher risk can contribute to developing early monitoring protocols and targeted therapy approaches.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379886","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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Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia. 基因未解决的原发性睫状肌运动障碍病例中导致等位基因特异性表达的启动子缺失。

IF 1.7 4区生物学

American Journal of Medical Genetics Part A Pub Date : 2024-10-04 DOI: 10.1002/ajmg.a.63880

M Makenzie Beaman, Weining Yin, Amanda J Smith, Patrick R Sears, Margaret W Leigh, Thomas W Ferkol, Brendan Kearney, Kenneth N Olivier, Adam J Kimple, Shannon Clarke, Erin Huggins, Erica Nading, Seung-Hye Jung, Apoorva K Iyengar, Xue Zou, Hong Dang, Alejandro Barrera, William H Majoros, Catherine W Rehder, Timothy E Reddy, Lawrence E Ostrowski, Andrew S Allen, Michael R Knowles, Maimoona A Zariwala, Gregory E Crawford

{"title":"Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia.","authors":"M Makenzie Beaman, Weining Yin, Amanda J Smith, Patrick R Sears, Margaret W Leigh, Thomas W Ferkol, Brendan Kearney, Kenneth N Olivier, Adam J Kimple, Shannon Clarke, Erin Huggins, Erica Nading, Seung-Hye Jung, Apoorva K Iyengar, Xue Zou, Hong Dang, Alejandro Barrera, William H Majoros, Catherine W Rehder, Timothy E Reddy, Lawrence E Ostrowski, Andrew S Allen, Michael R Knowles, Maimoona A Zariwala, Gregory E Crawford","doi":"10.1002/ajmg.a.63880","DOIUrl":"10.1002/ajmg.a.63880","url":null,"abstract":"Variation in the non-coding genome represents an understudied mechanism of disease and it remains challenging to predict if single nucleotide variants, small insertions and deletions, or structural variants in non-coding genomic regions will be detrimental. Our approach using complementary RNA-seq and targeted long-read DNA sequencing can prioritize identification of non-coding variants that lead to disease via alteration of gene splicing or expression. We have identified a patient with primary ciliary dyskinesia with a pathogenic coding variant on one allele of the SPAG1 gene, while the second allele appears normal by whole exome sequencing despite an autosomal recessive inheritance pattern. RNA sequencing revealed reduced SPAG1 transcript levels and exclusive allele specific expression of the known pathogenic allele, suggesting the presence of a non-coding variant on the second allele that impacts transcription. Targeted long-read DNA sequencing identified a heterozygous 3 kilobase deletion of the 5' untranslated region of SPAG1, overlapping the promoter and first non-coding exon. This non-coding deletion was missed by whole exome sequencing and gene-specific deletion/duplication analysis, highlighting the importance of investigating the non-coding genome in patients with \"missing\" disease-causing variation. This paradigm demonstrates the utility of both RNA and long-read DNA sequencing in identifying pathogenic non-coding variants in patients with unexplained genetic disease.","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370743","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