Shamseldin, Hanan E., Kurdi, Wesam, Almusafri, Fatima, Alnemer, Maha, Alkaff, Alya, Babay, Zeneb, Alhashem, Amal ORCID: 0000-0002-9668-7809, Tulbah, Maha, Alsahan, Nada, Khan, Rubina, Sallout, Bahauddin, Al Mardawi, Elham, Seidahmed, Mohamed Zain, Meriki, Niema, Alsaber, Yasser, Qari, Alya, Khalifa, Ola, Eyaid, Wafaa, Rahbeeni, Zuhair, Kurdi, Ahmed, Hashem, Mais, Alshidi, Tarfa, Al-Obeid, Eman, Abdulwahab, Firdous, Ibrahim, Niema, Ewida, Nour, El-Akouri, Karen, Al Mulla, Mariam, Ben-Omran, Tawfeg, Pergande, Matthias, Cirak, Sebahattin, Al Tala, Saeed, Shaheen, Ranad, Faqeih, Eissa and Alkuraya, Fowzan S. (2018). Molecular autopsy in maternal-fetal medicine. Genet. Med., 20 (4). S. 420 - 428. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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Abstract

Purpose: The application of genomic sequencing to investigate unexplained death during early human development, a form of lethality likely enriched for severe Mendelian disorders, has been limited.& para;& para;Methods: In this study, we employed exome sequencing as a molecular autopsy tool in a cohort of 44 families with at least one death or lethal fetal malformation at any stage of in utero development. Where no DNA was available from the fetus, we performed molecular autopsy by proxy, i.e., through parental testing.& para;& para;Results: Pathogenic or likely pathogenic variants were identified in 22 families (50%), and variants of unknown significance were identified in further 15 families (34%). These variants were in genes known to cause embryonic or perinatal lethality (ALPL, GUSB, SLC17A5, MRPS16, THSD1, PIEZO1, and CTSA), genes known to cause Mendelian phenotypes that do not typically include embryonic lethality (INVS, FKTN, MYBPC3, COL11A2, KRIT1, ASCC1, NEB, LZTR1, TTC21B, AGT, KLHL41, GFPT1, and WDR81) and genes with no established links to human disease that we propose as novel candidates supported by embryonic lethality of their orthologs or other lines of evidence (MS4A7, SERPINA11, FCRL4, MYBPHL, PRPF19, VPS13D, KIAA1109, MOCS3, SVOPL, FENI, HSPB11, KIF19, and EXOC3L2).& para;& para;Conclusion: Our results suggest that molecular autopsy in pregnancy losses is a practical and high-yield alternative to traditional autopsy, and an opportunity for bringing precision medicine to the clinical practice of perinatology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Shamseldin, Hanan E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurdi, WesamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Almusafri, FatimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alnemer, MahaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alkaff, AlyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Babay, ZenebUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alhashem, AmalUNSPECIFIEDorcid.org/0000-0002-9668-7809UNSPECIFIED
Tulbah, MahaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alsahan, NadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, RubinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sallout, BahauddinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Mardawi, ElhamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidahmed, Mohamed ZainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meriki, NiemaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alsaber, YasserUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qari, AlyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khalifa, OlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eyaid, WafaaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahbeeni, ZuhairUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurdi, AhmedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hashem, MaisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alshidi, TarfaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al-Obeid, EmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdulwahab, FirdousUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ibrahim, NiemaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ewida, NourUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Akouri, KarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Mulla, MariamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ben-Omran, TawfegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pergande, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Tala, SaeedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shaheen, RanadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faqeih, EissaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alkuraya, Fowzan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-192016
DOI: 10.1038/gim.2017.111
Journal or Publication Title: Genet. Med.
Volume: 20
Number: 4
Page Range: S. 420 - 428
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1530-0366
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DISCOVERY; MUTATIONS; IDENTIFICATION; VARIANTS; ETIOLOGYMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19201

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