A de novo 2.2 Mb recurrent 17q23.1q23.2 deletion unmasks novel putative regulatory non-coding SNVs associated with lethal lung hypoplasia and pulmonary hypertension: a case report

BMC Medical Genomics
Justyna A KarolakPaweł Stankiewicz

Abstract

Application of whole genome sequencing (WGS) enables identification of non-coding variants that play a phenotype-modifying role and are undetectable by exome sequencing. Recently, non-coding regulatory single nucleotide variants (SNVs) have been reported in patients with lethal lung developmental disorders (LLDDs) or congenital scoliosis with recurrent copy-number variant (CNV) deletions at 17q23.1q23.2 or 16p11.2, respectively. Here, we report a deceased newborn with pulmonary hypertension and pulmonary interstitial emphysema with features suggestive of pulmonary hypoplasia, resulting in respiratory failure and neonatal death soon after birth. Using the array comparative genomic hybridization and WGS, two heterozygous recurrent CNV deletions: ~ 2.2 Mb on 17q23.1q23.2, involving TBX4, and ~ 600 kb on 16p11.2, involving TBX6, that both arose de novo on maternal chromosomes were identified. In the predicted lung-specific enhancer upstream to TBX4, we have detected seven novel putative regulatory non-coding SNVs that were absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. Our findings further support a recently reported model of complex compound inheritance of LLDD in which b...Continue Reading

References

Oct 1, 1979·The Journal of Pediatrics·L E SwischukM J Ingman
Aug 17, 1999·Archives of Disease in Childhood. Fetal and Neonatal Edition·H J Porter
Dec 10, 1999·Human Molecular Genetics·M O DorschnerK Stephens
Jan 31, 2002·Trends in Genetics : TIG·Paweł Stankiewicz, James R Lupski
Nov 19, 2002·Current Opinion in Pediatrics·Elena Perez, Kathleen E Sullivan
Aug 16, 2003·Journal of Paediatrics and Child Health·D E OddD B Knight
Nov 14, 2003·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lorraine PotockiJames R Lupski
May 27, 2005·American Journal of Human Genetics·Andrew J SharpEvan E Eichler
Aug 8, 2006·American Journal of Medical Genetics. Part a·Wiktor BorozdinJürgen Kohlhase
Jan 9, 2008·American Journal of Human Genetics·Shay Ben-ShacharAnkita Patel
Jan 11, 2008·The New England Journal of Medicine·Lauren A WeissUNKNOWN Autism Consortium
Feb 16, 2010·Nature Genetics·Santhosh GirirajanEvan E Eichler
Aug 10, 2012·PLoS Genetics·Ripla AroraVirginia E Papaioannou
Sep 14, 2012·The New England Journal of Medicine·Santhosh GirirajanEvan E Eichler
Apr 18, 2013·Journal of Medical Genetics·Wilhelmina S Kerstjens-FrederikseRolf M F Berger
Oct 15, 2013·Cell·Denes HniszRichard A Young
Jan 25, 2014·American Journal of Medical Genetics. Part a·Hussam Al-KatebMarwan Shinawi
Jan 8, 2015·The New England Journal of Medicine·N WuF Zhang
Apr 23, 2015·American Journal of Medical Genetics. Part a·Anju ShuklaKatta M Girisha
Jan 11, 2016·American Journal of Human Genetics·Michael H DuyzendEvan E Eichler
Jan 1, 2015·Nature Reviews. Disease Primers·Donna M McDonald-McGinnAnne S Bassett
Jul 5, 2016·American Journal of Medical Genetics. Part a·Przemyslaw SzafranskiPaweł Stankiewicz
Dec 14, 2016·The New England Journal of Medicine·Jennifer E PoseyJames R Lupski
Aug 21, 2018·European Journal of Medical Genetics·Danique R M VlaskampConny M A van Ravenswaaij-Arts
Jan 15, 2019·American Journal of Human Genetics·Justyna A KarolakPaweł Stankiewicz
Mar 5, 2019·American Journal of Medical Genetics. Part a·Kendell GermanJames T Bennett

❮ Previous
Next ❯

Citations

May 11, 2021·European Journal of Human Genetics : EJHG·Emma M WadeTim Cundy
Jun 11, 2021·BMC Medical Genomics·Trenell J MosleyJennifer G Mulle
Jul 3, 2021·International Journal of Molecular Sciences·Olga V BalberovaRegina F Nasyrova
Jul 29, 2021·Respiratory Research·Justyna A KarolakPaweł Stankiewicz

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
light microscopy
biopsy
ChIP-seq

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.