Whole-exome sequence analysis highlights the role of unmasked recessive mutations in copy number variants with incomplete penetrance

European Journal of Human Genetics : EJHG
Matthieu EgloffValérie Malan

Abstract

Several hypotheses have been proposed to explain the phenotypic variability between parent and offspring carrying the same genomic imbalance, including unmasking of a recessive variant by a chromosomal deletion. Here, 19 patients with neurodevelopmental disorders harboring a rare deletion inherited from a healthy parent were investigated by whole-exome sequencing to search for SNV on the contralateral segment. This strategy allowed us to identify a candidate variant in two patients in the NUP214 and NCOR1 genes. This result demonstrates that the analysis of the genes included in non-deleted contralateral allele is a key point in the etiological investigation of patients harboring a deletion inherited from a parent. Finally, this strategy is also an interesting approach to identify new recessive intellectual disability genes.

References

Feb 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·D KraemerA Radu
Nov 1, 2002·Nature·Ola HermansonMichael G Rosenfeld
Aug 3, 2005·Journal of Medical Genetics·J C K Barber
Apr 17, 2008·Journal of Medical Genetics·S T SouthA R Brothman
Jan 20, 2012·European Journal of Human Genetics : EJHG·Ron HochstenbachEdwin Cuppen
Dec 13, 2012·Journal of Medical Genetics·Donna M McDonald-McGinnLoydie A Jerome-Majewska
Jul 19, 2013·European Journal of Human Genetics : EJHG·Céline Pebrel-RichardChristine Francannet
Jan 8, 2015·The New England Journal of Medicine·N WuF Zhang
Jan 8, 2015·Frontiers in Cellular Neuroscience·Gökhan ErtaylanAntonio Del Sol
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium

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Citations

Oct 27, 2018·Histochemistry and Cell Biology·Ramona Jühlen, Birthe Fahrenkrog
Feb 14, 2019·Human Genetics·Hanan E ShamseldinFowzan S Alkuraya
Sep 24, 2021·Nature Communications·Narendra Kumar ChunduriZuzana Storchova

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Methods Mentioned

BETA
Fluorescence
reverse-transcription PCR

Software Mentioned

PolyPhen
Ensembl
IgView
DECIPHER
ExAC browser
ExAC
Mutation Taster
browser
SIFT

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