Genetic variants of alpha-1-antitrypsin (AAT).
This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M-like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT.
Fabbretti
G
G
Department of Pathology and Molecular Genetics, Children's Hospital G. Gaslini Institute, Genoa, Italy.
Sergi
C
C
Consalez
G
G
Consales
G
G
Faa
G
G
Brisigotti
M
M
Romeo
G
G
Callea
F
F
D001483:Base Sequence; D005091:Exons; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D000515:alpha 1-Antitrypsin