Lifting the lid on unborn lethal Mendelian phenotypes through exome sequencing
Shamseldin, HE [ 1 ]; Swaid, A [ 2 ]; Alkuraya, FS [ 1,3,4,5 ]
GENETICS IN MEDICINE
Volume: 15, Issue: 4, Pages: 307-309, DOI: 10.1038/gim.2012.130, Published: APR
2013
Publisher NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY
10013-1917 USA
ISSN: 1098-3600
Abstract
Purpose: Mendelian phenotypes in humans vary from benign variants to lethal disorders.
Embryonic lethal phenotypes that are similar to what has been known for a long time in
mice have remained largely unknown because of the difficulty in arriving at a molecular
diagnosis. The purpose of this study is to test whether next generation sequencing can
reveal the underlying etiology of recurrent fetal loss.
Methods: We hypothesized that exome sequencing combined with autozygome analysis
can reveal the underlying mutation in a family in which recurrent fetal loss was likely to be
autosomal recessive in origin.
Results: A novel mutation in CHRNA1 was identified. This gene is known to cause
multiple pterygium and fetal akinesia syndrome.
Conclusion: This is the first report of exome sequencing to identify the cause of recurrent
fetal loss and reveal the diagnosis of a lethal human phenotype. Our results should
inspire a systematic examination of the extent of "unborn" Mendelian phenotypes in
humans using next-generation sequencing. Genet Med 2013:15(4):307-309
Keywords
Author Keywords:embryonic lethal; exome sequencing; hydrops fetalis; recurrent
abortion
KeyWords Plus:CAPTURE
Author Information
Reprint Address: Alkuraya, FS E-mail Addresses:falkuraya@kfshrc.edu.sa
King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
Organization-Enhanced Name(s)
King Faisal Specialist Hospital & Research Center
King Faisal Specialist Hospital & Research Center - Riyadh
Addresses:
[ 1 ] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia
Organization-Enhanced Name(s)
King Faisal Specialist Hospital & Research Center
King Faisal Specialist Hospital & Research Center - Riyadh
[ 2 ] King Abdul Aziz Med City, Dept Pediat, Riyadh, Saudi Arabia
Organization-Enhanced Name(s)
King Abdulaziz Medical City
King Abdulaziz Medical City - Riyadh
National Guard Health Affairs - Saudi Arabia
[ 3 ] King Saud Univ, King Khalid Univ Hosp, Dept Pediat, Riyadh, Saudi Arabia
Organization-Enhanced Name(s)
King Khalid University Hospital
King Saud University
[ 4 ] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia
Organization-Enhanced Name(s)
King Saud University
[ 5 ] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh, Saudi Arabia
Organization-Enhanced Name(s)
Alfaisal University