Article Text

PDF
Short report
Conotruncal malformations and absent thymus due to a deleterious NKX2-6 mutation
  1. Asaf Ta-Shma1,
  2. Nael El-lahham1,
  3. Simon Edvardson2,
  4. Polina Stepensky2,
  5. Amiram Nir1,
  6. Zeev Perles1,
  7. Sagui Gavri1,
  8. Julius Golender1,
  9. Nurit Yaakobi-Simhayoff1,
  10. Avraham Shaag2,
  11. Azaria J J T Rein1,
  12. Orly Elpeleg2
  1. 1Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  2. 2Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
  1. Correspondence Dr Asaf Ta-Shma, Department of Pediatric Cardiology, Hadassah Hebrew University Hospital, POB 12000 Ein-Karem, Jerusalem 91120, Israel; atashma{at}gmail.com

Abstract

Background Truncus arteriosus (TA) accounts for ∼1% of congenital heart defects. The aetiology of isolated TA is largely unknown but when occurring as part of a syndrome, it is mostly associated with chromosome 22q11 deletion. Vice versa, the most common congenital heart defects associated with chromosome 22q11 deletion are conotruncal malformations. In this study we investigated the cause of multiple conotruncal malformations accompanied by athymia in a consanguineous family.

Methods and results Whole exome analysis revealed a homozygous deleterious mutation in the NKX2-6 gene.

Conclusions NKX2-6 encodes a homeobox-containing protein which is expressed in mouse embryo at E8.0-E9.5 at the caudal pharyngeal arches and the outflow tract. A single missense mutation was previously implicated in the aetiology of familial isolated TA; however, null mice are entirely normal. The clear phenotype associated with a homozygous deleterious mutation in the present report, falls well within the spectrum of the cardiac defects seen in DiGeorge syndrome, is in agreement with NKX2-6 downstream location in the TBX1 signalling pathway and confirms NKX2-6 role in human cardiogenesis.

  • Congenital heart disease
  • Clinical genetics

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.