Whole-exome analysis of foetal autopsy tissue reveals a frameshift mutation in OBSL1, consistent with a diagnosis of 3-M Syndrome

BMC Genomics

Research

Adel M Abuzenadah¹  Muhammad Abu-Elmagd²  Tracy L Stockley³  Dimitri J Stavropoulos³  Peter N Ray³  Ronald D Cohn⁴  Donna Cushing⁵  Sandra A Farrell⁵  Richard F Wintle⁶  Lynette Lau⁶  Sergio L Pereira⁶  Tara Paton⁶  Michael Szego⁷  Christian R Marshall⁸  Stephen W Scherer⁹ 

[1] Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, 80216 Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, 80216 Jeddah, Kingdom of Saudi Arabia;KACST Technology Innovation Center in Personalized Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia;Zoology Department, Faculty of Science, Minia University, Minia, Egypt;Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, M5G 1X8, Toronto, Ontario, Canada;Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada;Genetics, Trillium Health Partners, Credit Valley Hospital, L5M 2N1, Mississauga, Ontario, Canada;The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, M5G 0A4, Toronto, Ontario, Canada;The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, M5G 0A4, Toronto, Ontario, Canada;Joint Centre for Bioethics and Department of Family and Community Medicine, the University of Toronto, M5T 1P8, Ontario, Canada;The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, M5G 0A4, Toronto, Ontario, Canada;McLaughlin Centre and Department of Molecular Genetics, the University of Toronto, M5S 2J7, Ontario, Canada;The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, M5G 0A4, Toronto, Ontario, Canada;McLaughlin Centre and Department of Molecular Genetics, the University of Toronto, M5S 2J7, Ontario, Canada;Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, 21589, 80216 Jeddah, Kingdom of Saudi Arabia;

关键词: exome sequencing;    frameshift mutation;    OBSL1;    skeletal dysplasia;    3-M Syndrome;   

DOI  :  10.1186/1471-2164-16-S1-S12

来源: Springer

【 摘 要 】

BackgroundWe report a consanguineous couple that has experienced three consecutive pregnancy losses following the foetal ultrasound finding of short limbs. Post-termination examination revealed no skeletal dysplasia, but some subtle proximal limb shortening in two foetuses, and a spectrum of mildly dysmorphic features. Karyotype was normal in all three foetuses (46, XX) and comparative genomic hybridization microarray analysis detected no pathogenic copy number variants.ResultsWhole-exome sequencing and genome-wide homozygosity mapping revealed a previously reported frameshift mutation in the OBSL1 gene (c.1273insA p.T425nfsX40), consistent with a diagnosis of 3-M Syndrome 2 (OMIM #612921), which had not been anticipated from the clinical findings.ConclusionsOur study provides novel insight into the early clinical manifestations of this form of 3-M syndrome, and demonstrates the utility of whole exome sequencing as a tool for prenatal diagnosis in particular when there is a family history suggestive of a recurrent set of clinical symptoms.

【 授权许可】

Unknown   
© Marshall et al; licensee BioMed Central Ltd. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.