Hereditary Angioedema Type III: type differentiation is crucial to survival for women

Alexandra ScottDepartment of BiologyUniversity of New Hampshire- Manchesteramc469@unh.edu


Background

In the past, scientists have been able to identify angioedema as an autosomal dominant trait present in both men and women. Further studies have proven that a deficiency in C1-inhibitor concentration is the heritable mutation that causes hereditary angioedema (HAE) type I and type II. Recently, in studies isolating female patients that demonstrate symptoms of HAE scientists noticed normal C1-inhibitor concentration (Bork et.al., 2000). The first observation made was an X-linked dominant trait passed from mother to offspring. The second observation made was an increased activity of Coagulation Factor XII or F12 (Bork et.al., 2000). This peaked the interest of many researchers to find the correlation. Figure 1 depicts one of the most serious side effects of HAE, laryngeal oedema of both tongue, throat and lips causes occlusion of the airway leading to asphyxiation and death.
Figure 1: Oedema of the lips and tongue in a 35 year old woman
please_work_oedema.png
Permission granted by Dr. Konrad Bork; source The Lancet, 356. doi:10.1016/j.physletb.2003.10.07

The purpose of this research was to gain knowledge of the clinical aspects involved in HAEIII, and assess itsgenetic basis. Therefore the questions I asked were:
  • what is an attack of HAEIII and how does it present?
  • what genetic factors play a role in its expression?
  • and what interventions and treatments can be used in an attack?
The links below are designed to introduce the disease, explore the genetic basis, and suggest future research and medical therapies based on known findings.





Signs and Symptoms: clinical features of HAE III

Bioinformatics; using genetic technology to understand the underlying cause

Discussion and Current protocol in diagnosing HAEIII







Annotated Bibliography

Bauer, Scott (2010). The Facts: Down on the Pharm; Agricultural Research Service. Popular Science: http://www.popsci.com/science/gallery/2010-07/facts-down-pharm
---Popular Science is a journal and online resource to new and upcoming science technology. This website was used to find the most recent news and research about HAE III.

Bork, K., Barnstedt, S.E., Koch, P., & Traupe, H. (2000). Hereditary angioedema with normal c1-inhibitor activity in women. The Lancet, 356. doi: doi:10.1016/j.physletb.2003.10.07
---This article I used because Dr. Konrad Bork was one of the first scientists to begin research of Hereditary Angioedema III

Bowen, T, & Bork, K. (2010). 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Proceedings of the Hereditary Angioedema- Management Consensus 2010, http://www.aacijournal.com/content/6/1/24 10.1186/1710-1492-6-24.
---This article gave an updated summary of the standard protocol for diagnosis and methods of treatment

Caen, J., & Wu, Q. (2010). Hageman factor, platelets and polyphosphates: early history and recent connection. Journal of Thrombosis and Haemostasis, 8(8), Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20456750 doi: 10.1111/j.1538-7836.2010.03893.x.
---This article was helpful in understanding the connection between F12 and the expression of HAE

Cichon, S., Martin, L., Hennies, H., & Nothen, M. (2006). Increased activity of coagulation factor XII (hageman factor) causes hereditary angioedema type III. The American Journal of Human Genetics, 79(6), Retrieved fromhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698720/?tool=pubmed
---This article presented phylogenies of women in a family diagnosed with Hereditary Angioedema III and observed the Hageman Factor (F12), as a causative agent in this disease.


Bioinformatic Tools Report

1. http://www.ncbi.nlm.nih.gov/omim/610619#610619Variants0004- Online Mendelian Inheritance in Man (OMIM): a database that hosts all known mendelian disorders and over 12,000 genes. OMIM focuses on relationships between genotype and phenotype.

2. http://www.ncbi.nlm.nih.gov/protein/P00748.2- NCBI's Protein: a searchable database for protein sequences including translations from annotated coding regions in GenBank.

3. http://www.uniprot.org/uniprot/P00748- UniProt: database that is searchable for protein sequences and displays all related information concerning function.

4. http://www.genecards.org/cgi-bin/carddisp.pl?gene=TYR&search=tyrosinase- GeneCard: a search engine for human genes that has compiled information from various sources and integrated them to give detailed information about each gene and it's function

5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698720/?tool=pubmed- PubMed: provided articles that contain genomic data in relation to a disease or disorder of interest in research.

6. http://ca.expasy.org/cgi-bin/nicezyme.pl?3.4.21.38- ExPASy: ExPASy's enzyme; a repository of information related to the nomenclature of enzymes.

7. http://uswest.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000131187;r=5:176829141-176836577- Ensembl: a genomic database browser that provides information concerning locations of genes along chromosomes.