# THE C1 INHIBITOR GENE AND HEREDITARY ANGIONEUROTIC EDEMA

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 1994 · $173,989

## Abstract

Hereditary angioneurotic edema (HANE) is a dominantly inherited disease
characterized by recurrent episodes of edema of the skin and mucous
membranes.  Involvement of the larynx may result in death due to
asphyxiation.  The disease occurs in individuals who are heterozygous for
deficiency of C1 inhibitor, a plasma protease inhibitor that regulates
activation of the complement and kinin-forming systems.  Deficiency may
result from lack of expression C1 inhibitor (type I) or from expression of
a dysfunctional mutant C1 inhibitor molecule (type II).  The overall goals
of the proposed project are to define the molecular genetic defects in the
C1 inhibitor gene that result in HANE, to delineate those structured
features of C1 inhibitor that are important for its function, and to
analyze the regulation of transcription of the C1 inhibitor gene.  The C1
inhibitor gene (or relevant portions thereof) from patients with both type
I and type II HANE will be cloned and sequenced.  About 15-20% of type I
result from deletions, all of which appear to be different from one
another.  Several of these will be characterized in order to define whether
they result from the same or different mechanisms.  Similarly, several
individuals from the larger group of type I patients without a deletion
will be analyzed to define the distribution of the types of mutations that
produce deficiency.  The analysis of defects resulting in dysfunctional C1
inhibitor (type II) will concentrate on those  with mutations outside the
active center arginine.  These dysfunctional proteins, and C1 INH modified
at the same sites in the molecule  by site directed mutagenesis, will be
expressed in vitro, and their function analyzed.  Other specific residues
thought to be of functional importance will be analyzed in the same way.
C1 inhibitor expressed in a prokaryotic system and eukaryotic expression of
C1 inhibitor truncated at its amino terminal end (which contains most of
the carbohydrate) will be used to define the role of carbohydrate in its
function.  As another probe of function, and autoantibody to C1 inhibitor
from a patient with acquired angioedema will be used to help define regions
of the molecule required for function.  The regulation of synthesis of C1
inhibitor by cytokines and androgens also will be examined and will lead to
study of promoters and enhancer elements in the C1 INH gene.  Definition of
synthesis regulation could lead to other therapeutic approaches aimed
toward enhancement of synthesis, but without the complications associated
with current therapy.

## Key facts

- **NIH application ID:** 2198443
- **Project number:** 5R01HD022082-09
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **SAM.gov UEI:** JZD1HLM2ZU83
- **Principal Investigator:** ALVIN E DAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $173,989
- **Award type:** 5
- **Project period:** 1987-04-01 → 1995-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198443

## Citation

> US National Institutes of Health, RePORTER application 2198443, THE C1 INHIBITOR GENE AND HEREDITARY ANGIONEUROTIC EDEMA (5R01HD022082-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198443. Licensed CC0.

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