Genetic analysis of<i>de novo</i>variants reveals sex differences in complex and isolated congenital diaphragmatic hernia and indicates<i>MYRF</i>as a candidate gene

Qi, Hongjian; Yu, Lan; Zhou, Xueya; Kitaygorodsky, Alexander; Wynn, Julia; Zhu, Na; Aspelund, Gudrun; Lim, FY; Crombleholme, Timothy M.; Cusick, Robert A.; Azarow, Kenneth S.; Danko, ME; Chung, Dai H.; Bw, Warner; Gb, Mychaliska; Potoka, Douglas A.; Wagner, Andreas; Elfiky, Mahmoud; Da, Nickerson; Bamshad, Mike; Jg, Wilson; Fa, High; Longoni, Mauro; Donahoe, Patricia K.; Chung, Wendy K.; Shen, Yufeng

doi:10.1101/206037

Cited by 5 publications

(4 citation statements)

References 50 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is some emerging evidence that there may be sex-related differences in the genetics of isolated CDH, with girls carrying more de novo coding variants; however, the correlation between genetic aetiology and CDH severity is as yet unclear 12. The reasons for the higher proportion of girls dying before operative repair of CDH merit further investigation.…”

Section: Discussionmentioning

confidence: 99%

Early population-based outcomes of infants born with congenital diaphragmatic hernia

Long

Bunch

Knight

et al. 2018

Arch Dis Child Fetal Neonatal Ed

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Early population-based outcomes of infants born with congenital diaphragmatic hernia

Long

Bunch

Knight

et al. 2018

Arch Dis Child Fetal Neonatal Ed

View full text Add to dashboard Cite

show abstract

“…Recent trio studies have reported DNMs in MYRF as candidates in congenital diaphragmatic hernia and congenital heart disease. 54,55 Most of them were damaging missense mutations located in the conserved DBD and ICD. Additionally, MYRF was identified during the course of constructing a transcript map of the region encompassing the BEST1 gene (OMIM 607854) and eye tissue-specific cDNA selection.…”

Section: Discussionmentioning

confidence: 99%

Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study

Guo

Zhao

Chen

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Guo C, Zhao Z, Chen D, et al. Detection of clinically relevant genetic variants in Chinese patients with nanophthalmos by trio-based wholegenome sequencing study. Invest Ophthalmol Vis Sci. 2019;60:2904-2913. https://doi.org/10.1167 PURPOSE. Nanophthalmos is a rare genetic disorder commonly characterized by a short axial length (AL) and severe hyperopia. Mutations that have been identified through Mendelian genetic analysis can only explain a fraction of nanophthalmic cases. We investigate the clinically relevant genetic variants in nanophthalmos by whole-genome sequencing (WGS), including de novo mutations (DNMs) and inherited mutations. METHODS.Clinically relevant genetic variants of 11 trios (11 nanophthalmic probands and their unaffected parents) from the Zhongshan Ophthalmic Center, China, were analyzed by WGS. We further screened three trios and 10 sporadic cases to identify the MYRF mutations.RESULTS. In two of 11 trios, without evidence of the presence of deleterious inherited autosomal variants, two DNMs of MYRF (c.789delC, p.S264fs and c.789dupC, p.S264fs) were identified in the probands. These loss-of-function DNMs were predicted to result in premature stop codons and protein structure damage in both probands. In addition, deleterious inherited genetic variants in PRSS56 and MFRP were found in eight probands of the other nine trios. Expanded screening found an additional MYRF DNM (c.1433G>C, p.R478P) in one trio and a stop-gain MYRF mutation (c.2956C>T, p.R986X) in one sporadic case, suggesting the recurrence of MYRF mutations in nanophthalmic patients.CONCLUSIONS. This is the first trio-based WGS study for nanophthalmos, revealing the potential role of DNMs in MYRF and rare inherited genetic variants in PRSS56 and MFRP. The underlying mechanism of MYRF in the development of nanophthalmos needs to be further investigated.

show abstract

“…Missense variants are the most abundant type of coding genetic variants and a major class of genetic risk in a broad range of common and rare diseases. Previous studies have estimated that there is substantial contribution from de novo missense mutations to structural birth defects [1][2][3][4][5] , and neurodevelopmental disorders [6][7][8] .…”

Section: Main Textmentioning

confidence: 99%

MVP: predicting pathogenicity of missense variants by deep learning

Chen

Zhang

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Accurate pathogenicity prediction of missense variants is critical to improve power in genetic studies and accurate interpretation in clinical genetic testing. Here we describe a new prediction method, MVP, which uses a deep learning approach to leverage large training data sets and many correlated predictors. Using cancer mutation hotspots and de novo germline mutations from developmental disorders for benchmarking, MVP achieved better performance in prioritizing pathogenic missense variants than previous methods.

show abstract

Genetic analysis ofde novovariants reveals sex differences in complex and isolated congenital diaphragmatic hernia and indicatesMYRFas a candidate gene

Abstract: Congenital diaphragmatic hernia

Cited by 5 publications

References 50 publications

Early population-based outcomes of infants born with congenital diaphragmatic hernia

Early population-based outcomes of infants born with congenital diaphragmatic hernia

Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study

MVP: predicting pathogenicity of missense variants by deep learning

Contact Info

Product

Resources

About