Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Hum Genet. 2010 Sep 10;87(3):436-44. doi: 10.1016/j.ajhg.2010.08.008.

Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans.

Author information

  • 1Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.

Abstract

The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers and the study of congenital lymphedema syndromes. We report the results of genetic analyses of a kindred inheriting a unique autosomal-recessive lymphedema-choanal atresia syndrome. These studies establish linkage of the trait to chromosome 1q32-q41 and identify a loss-of-function mutation in PTPN14, which encodes a nonreceptor tyrosine phosphatase. The causal role of PTPN14 deficiency was confirmed by the generation of a murine Ptpn14 gene trap model that manifested lymphatic hyperplasia with lymphedema. Biochemical studies revealed a potential interaction between PTPN14 and the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. These results suggest a unique and conserved role for PTPN14 in the regulation of lymphatic development in mammals and a nonconserved role in choanal development in humans.

2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PMID:
20826270
[PubMed - indexed for MEDLINE]
PMCID:
PMC2933336
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk