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Genet Med. 2013 Apr;15(4):307-9. doi: 10.1038/gim.2012.130. Epub 2012 Oct 4.

Lifting the lid on unborn lethal Mendelian phenotypes through exome sequencing.

Author information

1
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

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.

PMID:
23037934
PMCID:
PMC3908556
DOI:
10.1038/gim.2012.130
[Indexed for MEDLINE]
Free PMC Article

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