Jake Gluckman, Tess Levy, Kate Friedman, Francesca Garces, Rajna Filip-Dhima, Aisling Quinlan, Isabelle Iannotti, Margaret Pekar, Alexandra Lopez Hernandez, Madison T. Nava, Elijah Kravets, Abigail Siegel, Jonathan A. Bernstein, Elizabeth Berry-Kravis, Craig M. Powell, Latha Valluripalli Soorya, Audrey Thurm, Siddharth Srivastava, Joseph D. Buxbaum, Mustafa Sahin, Alexander Kolevzon, Bruce D. Gelb, the Developmental Synaptopathies Consortium
{"title":"Aortic Root Dilation and Genotype Associations in Phelan-McDermid Syndrome","authors":"Jake Gluckman, Tess Levy, Kate Friedman, Francesca Garces, Rajna Filip-Dhima, Aisling Quinlan, Isabelle Iannotti, Margaret Pekar, Alexandra Lopez Hernandez, Madison T. Nava, Elijah Kravets, Abigail Siegel, Jonathan A. Bernstein, Elizabeth Berry-Kravis, Craig M. Powell, Latha Valluripalli Soorya, Audrey Thurm, Siddharth Srivastava, Joseph D. Buxbaum, Mustafa Sahin, Alexander Kolevzon, Bruce D. Gelb, the Developmental Synaptopathies Consortium","doi":"10.1002/ajmg.a.63872","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the <i>SHANK3</i> gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (<i>p</i> = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (<i>p</i> = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.</p>\n </div>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"197 1","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Medical Genetics Part A","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.63872","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.
期刊介绍:
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .