Identification of a Pathogenic TGFBR2 Variant in a Patient With Loeys-Dietz Syndrome

Frontiers in Genetics
Xi LuoFeng Zhu

Abstract

Loeys-Dietz syndrome (LDS) is a rare connective tissue genetic disorder that is caused by a pathogenic variant in genes of transforming growth factor (TGF) beta receptor 1 (TGFBR1), TGFBR2, mothers against decapentaplegic homolog 2 (SMAD2), SMAD3, TGFB2, or TGFB3. It is characterized by aggressive vascular pathology, aneurysms, arterial tortuosity, bifid uvula, hypertelorism, and cleft palate. Here we present a 42-year-old female patient with LDS. The patient underwent rapidly progressing artery aneurysms and life-threatening aortic dissection. Spontaneous fracture of the first metatarsal bone was noted in her medical record. Physical examination revealed a delayed wound healing on her left abdomen. Considering these clinical manifestations, we speculated that there was a genetic defect in the connective tissue, which provides strength and flexibility to structures such as bones, skins, ligaments, and blood vessels. Thus, whole exome sequencing (WES) was performed on the proband and revealed a heterozygous missense pathogenic variant (c.1613T > C/p.Val538Ala) in TGFBR2, which was a de novo variant in the proband as confirmed by the segregation analysis in parental samples. Although this variant was discovered and associated wit...Continue Reading

References

Jun 26, 2003·Nucleic Acids Research·Pauline C Ng, Steven Henikoff
Aug 9, 2005·Neuromuscular Disorders : NMD·Susan TrevesFrancesco Zorzato
Aug 25, 2006·The New England Journal of Medicine·Bart L LoeysHarry C Dietz
Sep 2, 2008·Nature Cell Biology·Alessandro SorrentinoMaréne Landström
Oct 15, 2008·The American Journal of Surgical Pathology·Joseph J MaleszewskiMarc K Halushka
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Oct 29, 2009·Human Mutation·Paula L HedleyMichael Christiansen
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Dec 15, 2010·PLoS Computational Biology·Eugene V DavydovSerafim Batzoglou
May 20, 2011·Nature·Mark E Lindsay, Harry C Dietz
Feb 14, 2012·The Journal of Clinical Investigation·Jun-ichi IwataYang Chai
May 16, 2012·Genome Research·Niklas KrummEvan E Eichler
Apr 16, 2013·International Journal of Cardiology·Romy FrankenBarbara J M Mulder
Mar 1, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Gretchen MacCarrickHarry C Dietz
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 4, 2015·Journal of the American College of Cardiology·Aida M Bertoli-AvellaBart L Loeys
Feb 16, 2016·Clinica Chimica Acta; International Journal of Clinical Chemistry·Mingyao LuoQian Chang
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Jan 31, 2017·American Journal of Human Genetics·Quan Li, Kai Wang
Jul 25, 2018·International Journal of Molecular Sciences·Norifumi TakedaIssei Komuro
Sep 18, 2018·American Journal of Human Genetics·Najmeh AlirezaieToby Dylan Hocking
Jan 8, 2019·The Journal of Clinical Investigation·Elena Gallo MacFarlaneHarry C Dietz
Feb 15, 2019·Circulation Research·Amélie PinardDianna M Milewicz

❮ Previous
Next ❯

Citations

Mar 9, 2021·European Journal of Pediatric Surgery Reports·Annie Le-NguyenMichel Lallier

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
exome sequencing
dissect
PCR
electrophoresis

Software Mentioned

ANNOVAR
Phenolyzer
Polyphen2
MutationTaster
GERP
Clinvar
clinPred
CoNIFER
Genomic Evolutionary Rate Profiling ( GERP + + )
AMBER

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Aneurysm

Aneurysms are outward distensions or bulges that occurs in a weakened wall of blood vessels. Discover the latest research on aneurysms here.

Related Papers

Annals of Thoracic and Cardiovascular Surgery : Official Journal of the Association of Thoracic and Cardiovascular Surgeons of Asia
Yoshimasa SeikeHitoshi Ogino
European Journal of Pediatrics
Teck Wah TingTeng Hong Tan
© 2022 Meta ULC. All rights reserved