New Insight into the Genotype-Phenotype Correlation of <i>PRPH2</i>-Related Diseases Based on a Large Chinese Cohort and Literature Review by Yingwei Wang, Junwen Wang, Yi Jiang, Di Zhu, Jiamin Ouyang, Zhen Yi, Shiqiang Li, Xiaoyun Jia, Xueshan Xiao, Wenmin Sun, Panfeng Wang, Qingjiong Zhang

“…All variants were classified based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. …”
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A catalog of the genetic causes of hereditary angioedema in the Canary Islands (Spain) by Alejandro Mendoza-Alvarez, Eva Tosco-Herrera, Adrian Muñoz-Barrera, Luis A. Rubio-Rodríguez, Aitana Alonso-Gonzalez, Aitana Alonso-Gonzalez, Almudena Corrales, Almudena Corrales, Antonio Iñigo-Campos, Lourdes Almeida-Quintana, Elena Martin-Fernandez, Dara Martinez-Beltran, Eva Perez-Rodriguez, Ariel Callero, Jose C. Garcia-Robaina, Rafaela González-Montelongo, Itahisa Marcelino-Rodriguez, Itahisa Marcelino-Rodriguez, Jose M. Lorenzo-Salazar, Carlos Flores, Carlos Flores, Carlos Flores, Carlos Flores

“…Altogether, the diagnostic yield by assessing previously reported causal genes and considering variant reclassifications according to the American College of Medical Genetics guidelines reached 66.7% (95% Confidence Interval [CI]: 30.1-91.0) in families with more than one affected member and 10.0% (95% CI: 1.8-33.1) among cases without family information for the disease. …”
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FHLdb: A Comprehensive Database on the Molecular Basis of Familial Hemophagocytic Lymphohistiocytosis by Laura Viñas-Giménez, Laura Viñas-Giménez, Natàlia Padilla, Laura Batlle-Masó, Laura Batlle-Masó, Ferran Casals, Jacques G. Rivière, Jacques G. Rivière, Mónica Martínez-Gallo, Mónica Martínez-Gallo, Xavier de la Cruz, Xavier de la Cruz, Roger Colobran, Roger Colobran, Roger Colobran

“…All genetic variants have been classified as pathogenic, likely pathogenic, uncertain significance, likely benign or benign, according to the American College of Medical Genetics guidelines. Additionally, it integrates information from other relevant databases: clinical evidence from ClinVar and UniProt, population allele frequency from ExAC and gnomAD, and pathogenicity predictions from well-recognized tools (e.g., PolyPhen-2, SIFT). …”
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Comprehensive Assessment of BARD1 Messenger Ribonucleic Acid Splicing With Implications for Variant Classification by Logan C. Walker, Vanessa Lilian Lattimore, Anders Kvist, Petra Kleiblova, Petra Kleiblova, Petra Zemankova, Lucy de Jong, George A. R. Wiggins, Christopher Hakkaart, Simone L. Cree, Raquel Behar, Claude Houdayer, kConFab Investigators, kConFab Investigators, Michael T. Parsons, Martin A. Kennedy, Amanda B. Spurdle, Miguel de la Hoya

“…We present the most comprehensive assessment of BARD1 messenger RNA splicing, and demonstrate the application of these data for the classification of truncating and splice site variants according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines.Methods: Nanopore sequencing, short-read RNA-seq (whole transcriptome and targeted), and capillary electrophoresis analysis were performed by four laboratories to investigate alternative BARD1 splicing in blood, breast, and fimbriae/ovary related specimens from non-cancer affected tissues. …”
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Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy by Miriam Kessi, Miriam Kessi, Juan Xiong, Juan Xiong, Liwen Wu, Liwen Wu, Lifen Yang, Lifen Yang, Fang He, Fang He, Chen Chen, Chen Chen, Nan Pang, Nan Pang, Haolin Duan, Haolin Duan, Wen Zhang, Wen Zhang, Ahmed Arafat, Ahmed Arafat, Fei Yin, Fei Yin, Jing Peng, Jing Peng

“…Importantly, the known predictors are largely from the same ethnic group; hence, they lack replication.Purpose: We aimed to determine and investigate the diagnostic yield of CNV tests, new causative CNVs, and the independent predictors of significant CNVs in Chinese children with unexplained ID/GDD-EP.Materials and methods: A total of 100 pediatric patients with unexplained ID/GDD-EP and 1,000 healthy controls were recruited. The American College of Medical Genetics guideline was used to classify the CNVs. …”
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Implementation of Exome Sequencing in Clinical Practice for Neurological Disorders by María Isabel Alvarez-Mora, Laia Rodríguez-Revenga, Meritxell Jodar, Miriam Potrony, Aurora Sanchez, Celia Badenas, Josep Oriola, José Luis Villanueva-Cañas, Esteban Muñoz, Francesc Valldeoriola, Ana Cámara, Yaroslau Compta, Mar Carreño, María Jose Martí, Raquel Sánchez-Valle, Irene Madrigal

“…Nowadays, recommendations of the American College of Medical Genetics and Genomics strongly recommend applying next generation sequencing (NGS) as a first-line test in patients with these disorders. …”
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Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomesResearch... by Werner F. Blum, Jürgen Klammt, Serge Amselem, Heike M. Pfäffle, Marie Legendre, Marie-Laure Sobrier, Marie-Pierre Luton, Christopher J. Child, Christine Jones, Alan G. Zimmermann, Charmian A. Quigley, Gordon B. Cutler, Jr, Cheri L. Deal, Jan Lebl, Ron G. Rosenfeld, John S. Parks, Roland W. Pfäffle

“…DNA variants were classified as pathogenic according to the recommendations of the American College of Medical Genetics and Genomics. Demographic, auxologic, and endocrine data at baseline and during GH treatment were documented and related to the genotyping results. …”
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Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome by Qian Zhang, Qian Zhang, Shuya Yang, Xin Chen, Xin Chen, Hongdan Wang, Hongdan Wang, Keyan Li, Chaonan Zhang, Shixiu Liao, Shixiu Liao, Litao Qin, Litao Qin, Qiaofang Hou, Qiaofang Hou, Qiaofang Hou

“…The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. …”
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HLA-based banking of induced pluripotent stem cells in Saudi Arabia by Maryam Alowaysi, Robert Lehmann, Mohammad Al-Shehri, Moayad Baadhaim, Hajar Alzahrani, Doaa Aboalola, Asima Zia, Dalal Malibari, Mustafa Daghestani, Khaled Alghamdi, Ali Haneef, Dunia Jawdat, Fahad Hakami, David Gomez-Cabrero, Jesper Tegner, Khaled Alsayegh

“…The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. …”
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Molecular analysis and prenatal diagnosis of seven Chinese families with genetic epilepsy by Bin Mao, Bin Mao, Na Lin, Na Lin, Danhua Guo, Danhua Guo, Deqin He, Deqin He, Huili Xue, Huili Xue, Lingji Chen, Lingji Chen, Qianqian He, Qianqian He, Min Zhang, Min Zhang, Meihuan Chen, Meihuan Chen, Hailong Huang, Hailong Huang, Liangpu Xu, Liangpu Xu

“…A total of six variants (c.1408T&gt;G in ALDH7A1, c.1994_1997del in CDKL5, c.794G&gt;A in QARS1, c.2453C&gt;T in GRIN2A, and c.217dup and c.863+995_998+1480del in MFSD8) have not yet been reported to be associated with diseases and were all evaluated to be pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines.MethodsBased on the molecular findings, we have associated the intragenic deletion in MFSD8 with the mutagenesis mechanism of Alu-mediated genomic rearrangements for the first time and provided genetic counseling, medical suggestions, and prenatal diagnosis for the families. …”
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Delayed Puberty Due to a WDR11 Truncation at Its N-Terminal Domain Leading to a Mild Form of Ciliopathy Presenting With Dissociated Central Hypogonadism: Case Report by Sebastián Castro, Franco G. Brunello, Franco G. Brunello, Gabriela Sansó, Gabriela Sansó, Paula Scaglia, Paula Scaglia, María Esnaola Azcoiti, María Esnaola Azcoiti, Agustín Izquierdo, Agustín Izquierdo, Florencia Villegas, Ignacio Bergadá, María Gabriela Ropelato, María Gabriela Ropelato, Marcelo A. Martí, Rodolfo A. Rey, Rodolfo A. Rey, Rodolfo A. Rey, Romina P. Grinspon

“…The variant was predicted to undergo nonsense-mediated decay and classified as probably pathogenic following the American College of Medical Genetics and Genomics (ACMG) criteria. …”
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CFTR pathogenic variants spectrum in a cohort of Mexican patients with cystic fibrosis by Angélica Martínez-Hernández, Elvia C. Mendoza-Caamal, Namibia G. Mendiola-Vidal, Francisco Barajas-Olmos, José Rafael Villafan-Bernal, Juan Luis Jiménez-Ruiz, Tulia Monge-Cazares, Humberto García-Ortiz, Cecilia Contreras- Cubas, Federico Centeno-Cruz, Carmen Alaez-Verson, Soraya Ortega-Torres, Adriana del C. Luna-Castañeda, Vicente Baca, José Luis Lezana, Lorena Orozco

“…The use of different in silico software and American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) criteria allowed us to assume that all of these PVs were pathogenic, causing a severe phenotype. …”
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Prenatal Diagnosis of Fetuses With Increased Nuchal Translucency by Genome Sequencing Analysis by Kwong Wai Choy, Kwong Wai Choy, Kwong Wai Choy, Huilin Wang, Mengmeng Shi, Jingsi Chen, Zhenjun Yang, Rui Zhang, Huanchen Yan, Yanfang Wang, Shaoyun Chen, Matthew Hoi Kin Chau, Ye Cao, Ye Cao, Olivia Y.M. Chan, Yvonne K. Kwok, Yuanfang Zhu, Min Chen, Tak Yeung Leung, Tak Yeung Leung, Tak Yeung Leung, Zirui Dong, Zirui Dong, Zirui Dong

“…Detection of single-nucleotide variants, copy number variants, and structural rearrangements was performed simultaneously, and the results were integrated for interpretation in accordance with the guidelines of the American College of Medical Genetics and Genomics. Pathogenic or likely pathogenic (P/LP) variants were selected for validation and parental confirmation, when available.Results: Overall, 50 fetuses were enrolled, including 34 cases with isolated increased NT and 16 cases with other fetal structural malformations. …”
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Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer’s disease patients with pathogenic/likely pathogenic amyloid protein precursor mutations... by Yingzi Liu, Xuewen Xiao, Hui Liu, Xinxin Liao, Xinxin Liao, Xinxin Liao, Xinxin Liao, Xinxin Liao, Yafang Zhou, Yafang Zhou, Yafang Zhou, Yafang Zhou, Yafang Zhou, Ling Weng, Ling Weng, Ling Weng, Ling Weng, Ling Weng, Lu Zhou, Xixi Liu, Xiang-yun Bi, Tianyan Xu, Yuan Zhu, Qijie Yang, Sizhe Zhang, Xiaoli Hao, Weiwei Zhang, Weiwei Zhang, Weiwei Zhang, Weiwei Zhang, Weiwei Zhang, Junling Wang, Junling Wang, Junling Wang, Junling Wang, Junling Wang, Bin Jiao, Bin Jiao, Bin Jiao, Bin Jiao, Bin Jiao, Lu Shen, Lu Shen, Lu Shen, Lu Shen, Lu Shen, Lu Shen

“…In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines. …”
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CACNA1A Mutations Associated With Epilepsies and Their Molecular Sub-Regional Implications by Xue-Lian Li, Xue-Lian Li, Zong-Jun Li, Xiao-Yu Liang, De-Tian Liu, Mi Jiang, Liang-Di Gao, Huan Li, Xue-Qing Tang, Yi-Wu Shi, Bing-Mei Li, Na He, Bin Li, Wen-Jun Bian, Yong-Hong Yi, Chuan-Fang Cheng, Chuan-Fang Cheng, Jie Wang

“…The eight de novo mutations were evaluated as pathogenic or likely pathogenic mutations according to the criteria of American College of Medical Genetics and Genomics (ACMG). The frequencies of the compound heterozygous CACNA1A mutations identified in this cohort were significantly higher than that in the controls of East Asian and all populations (P = 7.30 × 10–4, P = 2.53 × 10–4). …”
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Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls by Jung Kim, Wen Luo, Mingyi Wang, Talia Wegman-Ostrosky, Megan N. Frone, Jennifer J. Johnston, Michael L. Nickerson, Melissa Rotunno, Shengchao A. Li, Maria I. Achatz, Seth A. Brodie, Michael Dean, Kelvin C. de Andrade, Fernanda P. Fortes, Matthew Gianferante, Payal Khincha, Mary L. McMaster, Lisa J. McReynolds, Alexander Pemov, Maisa Pinheiro, Karina M. Santiago, Blanche P. Alter, Neil E. Caporaso, Shahinaz M. Gadalla, Lynn R. Goldin, Mark H. Greene, Jennifer Loud, Xiaohong R. Yang, Neal D. Freedman, Susan M. Gapstur, Mia M. Gaudet, Donato Calista, Paola Ghiorzo, Maria Concetta Fargnoli, Eduardo Nagore, Ketty Peris, Susana Puig, Maria Teresa Landi, Belynda Hicks, Bin Zhu, Jia Liu, Joshua N. Sampson, Stephen J. Chanock, Lisa J. Mirabello, Lindsay M. Morton, Leslie G. Biesecker, Margaret A. Tucker, Sharon A. Savage, Alisa M. Goldstein, Douglas R. Stewart

“…Abstract Background Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8–5%. …”
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Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study by Alison M. Elliott, Shelin Adam, Christèle du Souich, Anna Lehman, Tanya N. Nelson, Clara van Karnebeek, Emily Alderman, Linlea Armstrong, Gudrun Aubertin, Katherine Blood, Cyrus Boelman, Cornelius Boerkoel, Karla Bretherick, Lindsay Brown, Chieko Chijiwa, Lorne Clarke, Madeline Couse, Susan Creighton, Abby Watts-Dickens, William T. Gibson, Harinder Gill, Maja Tarailo-Graovac, Sara Hamilton, Harindar Heran, Gabriella Horvath, Lijia Huang, Gurdip K. Hulait, David Koehn, Hyun Kyung Lee, Suzanne Lewis, Elena Lopez, Kristal Louie, Karen Niederhoffer, Allison Matthews, Kirsten Meagher, Junran J. Peng, Millan S. Patel, Simone Race, Phillip Richmond, Rosemarie Rupps, Ramona Salvarinova, Kimberly Seath, Kathryn Selby, Michelle Steinraths, Sylvia Stockler, Kaoru Tang, Christine Tyson, Margot van Allen, Wyeth Wasserman, Jill Mwenifumbo, Jan M. Friedman

“…The variants observed were interpreted by a multidisciplinary team including laboratory geneticists, bioinformaticians, clinical geneticists, genetic counselors, pediatric subspecialists, and the referring physician, and independently by a clinical laboratory using standard American College of Medical Genetics and Genomics (ACMG) criteria. …”
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A Roadmap to Newborn Screening for Duchenne Muscular Dystrophy by Samiah A. Al-Zaidy, Michele Lloyd-Puryear, Annie Kennedy, Veronica Lopez, Jerry R. Mendell

“…The effort includes a formalized national Duchenne Newborn Screening Steering Committee, six related Working Groups, a Duchenne Screening Test Development Project led by PerkinElmer, a program with the American College of Medical Genetic and Genomics’ Newborn Screening Translation Research Network (NBSTRN), and collaborations with other Duchenne partners and federal agencies involved in NBS. …”
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Identification of two novel and one rare mutation in DYRK1A and prenatal diagnoses in three Chinese families with intellectual Disability-7 by Cheng Huang, Haiyan Luo, Baitao Zeng, Chuanxin Feng, Jia Chen, Huizhen Yuan, Shuhui Huang, Bicheng Yang, Yongyi Zou, Yanqiu Liu

“…In light of the updated American College of Medical Genetic and Genomics (ACMG) criterion, the variant of exon3_exon4del and c.1159C&gt;T were both classified as likely pathogenic (PSV1+PM6), while c1309C&gt;T was identified as pathogenic (PVS1+PS2_Moderate+PM2). …”
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