Pathogenesis of Unexplained Drowning: New Insights From a Molecular Autopsy

Tester, David J.; Kopplin, Laura J.; Creighton, Wendy; Burke, Allen P.; Ackerman, Michael J.
May 2005
Mayo Clinic Proceedings;May2005, Vol. 80 Issue 5, p596
Academic Journal
OBJECTIVE: To perform a molecular autopsy Involving the RyR2-encoded cardiac ryanodine receptor/calcium release channel to determine whether mutations responsible for catecholaminergic polymorphic ventricular tachycardla (CPVT) represent a novel pathogenic basis for unexplained drownings. METHODS: A cardiac channel molecular autopsy was performed on 2 individuals who died of unexplained drowning and whose cases were referred to the Sudden Death Genomics Laboratory at the Mayo Clink in Rochester Minn. Comprehensive mutational analysis of all 60 protein-encoded exons of the 5 long QT syndrome- causing cardiac channel genes and a targeted analysis of 18 RyR2 exons known to host RyR2-medilated CPVT-causing mutations (CPVT1) was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. RESULTS: Both Individuals harbored novel mutations In RyR2. Postmortem mutational analysis revealed a familial missense mutation in non 14, R414C, in a 16-year-old girl. A 9-year-old boy possessed a sporadic missense mutation in exon 49, V2475F. Both amino acid positions involve highly conserved residues that localize to critical functional domains in the calcium release channel. Neither substitution was present in 1000 reference shies. CONCLUSIONS: This molecular autopsy study provides proof of principle that RyR2 mutations can underlie some unexplained drownings. A population-based genetic epidemiology study that Involves molecular autopsies of individuals who die of unexplained drowning Is needed to determine the prevalence and spectrum of KCNQ1 and now RyR2 mutations as potential pathogenic mechanisms for drowning.


Related Articles

  • BRCA1 testing for the Scottish Molecular Genetics Consortium. Gregory, Helen; Bell, C. // Journal of Medical Genetics;Sep2003 Supplement, Vol. 40, pS69 

    Testing for BRCA1 in the Scottish Molecular Genetics Consodium Laboratories began in May 2001. Data is presented for testing performed in Aberdeen to date, but does not include mutations found in Scotland prior to May 2001. 143 samples taken from affected individuals in high risk breast or...

  • Minority HIV-1 Drug Resistance Mutations Are Present in Antiretroviral TreatmentNave Populations and Associate with Reduced Treatment Efficacy. Johnson, Jeffrey A.; Li, Jin-Fen; Wei, Xierong; Lipscomb, Jonathan; Irlbeck, David; Craig, Charles; Smith, Amanda; Bennett, Diane E.; Monsour, Michael; Sandstrom, Paul; Lanier, E. Randall; Heneine, Walid // PLoS Medicine;Jul2007, Vol. 5 Issue 7, pe158 

    Using real-time PCR to detect HIV resistance mutations present at low levels, Jeffrey Johnson and colleagues investigate prevalence and clinical implications of minority transmitted mutations.

  • RB1 GENE MUTATIONS AT POCKET B OF E1A DOMAIN AND CLINICAL PRESENTATION OF RETINOBLASTOMA CHILDREN IN MALAYSIA. I., Siti Raihan; H., Hanani; A., Joseph; A. G., Shuaibah; I., Shatriah; P. S., Lai; A. T., Liza Sharmini; B. A., Zilfalil // Malaysian Journal of Medical Sciences;Jan2008 Supplement, p23 

    Objective: To determine the presence of exon 20 to 22 (pocket B E1A Domain) mutations of RB1 gene and their clinical presentation in Malaysian children with retinoblastoma. Patients and Method: Children with retinoblastoma from two main tertiary centers in Malaysia, Hospital Universiti Sains...

  • Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients. Mihalatos, Markos; Apessos, Angela; Dauwerse, Hans; Velissariou, Voula; Psychias, Aristidis; Koliopanos, Alexander; Petropoulos, Konstantinos; Triantafillidis, John K.; Danielidis, Ioannis; Fountzilas, George; Agnantis, Niki J.; Nasioulas, Georgios // BMC Cancer;2005, Vol. 5, p40 

    Background: Familial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations are point mutations or small insertions / deletions which lead to truncated protein products. Splicing mutations or gross genomic...

  • High-Throughput Vector-Borne Disease Environmental Surveillance By Polymerase Chain Reaction According To International Accreditation Requirements. Soehnlen, Marty K.; Crimmins, Stephen L.; Clugston, Andrew S.; Gruhn, Nina; Gomez, Carlos J.; Cross, Michael E.; Statham, Charles N. // U.S. Army Medical Department Journal;Jul-Sep2014, p21 

    Although vector-borne diseases are specific to the region of the host, there is a necessity for surveillance or reference laboratories to perform standardized, high-throughput testing capable of meeting the needs of a changing military environment and response efforts. The development of...

  • Laboratory Diagnosis of Four Recent Sporadic Cases of Community-acquired SARS, Guangdong Province, China. Guodong Liang; Qiuxia Chen; Jianguo Xu; Yufei Liu; Wilina Lim; Peiris, J. S. M.; Anderson, Larry J.; Li Ruan; Hui Li; Biao Kan; Biao Di; Cheng, Peter; Chan, K. H.; Erdman, Dean D.; Shuyan Gu; Xinge Yan; Weili Liang; Duanhua Zhou; Haynes, Lia; Shumin Duan // Emerging Infectious Diseases;Oct2004, Vol. 10 Issue 10, p1774 

    Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China...

  • Human Coronavirus Infections in Rural Thailand: A Comprehensive Study Using Real-Time Reverse- Transcription Polymerase Chain Reaction Assays. Dare, Ryan K.; Fry, Alicia M.; Chittaganpitch, Malinee; Sawanpanyalert, Pathom; Olsen, Sonja J.; Erdman, Dean D. // Journal of Infectious Diseases;11/1/2007, Vol. 196 Issue 9, p1321 

    Background. We sought to determine whether infections with human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are associated with pneumonia and to define the epidemiology of HCoV infection in rural Thailand. Methods. We developed a real-time reverse-transcription polymerase chain reaction...

  • Highly-Sensitive Allele-Specific PCR Testing Identifies a Greater Prevalence of Transmitted HIV Drug Resistance in Japan. Nishizawa, Masako; Hattori, Junko; Shiino, Teiichiro; Matano, Tetsuro; Heneine, Walid; Johnson, Jeffrey A.; Sugiura, Wataru // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Background:The transmission of drug-resistant HIV in newly identified infected populations has become an underlying epidemic which can be better assessed with sensitive resistance testing. Since minority drug resistant variants cannot be detected by bulk sequencing, methods with improved...

  • Early detection and quantification of lamivudine-resistant hepatitis B virus mutants by fluorescent biprobe hybridization assay in lamivudine-treated patients. Umeoka, Fumi; Iwasaki, Yoshiaki; Matsumura, Masayuki; Takaki, Akinobu; Kobashi, Haruhiko; Tatsukawa, Masashi; Shiraha, Hidenori; Fujioka, Shin-ichi; Sakaguchi, Kohsaku; Shiratori, Yasushi // Journal of Gastroenterology;Jul2006, Vol. 41 Issue 7, p693 

    Long-term lamivudine treatment induces the emergence of lamivudine-resistant hepatitis B virus (HBV). The objective of this study was to develop a fluorescent biprobe hybridization (FBH) assay for the detection and quantification of HBV mutants in the clinical course of lamivudine-treated...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics