Spectrin Oran (alpha II/21), a new spectrin variant concerning the alpha II
domain and causing severe elliptocytosis in the homozygous state
N Alloisio, L Morle, B Pothier, AF Roux, J Marechal, MT Ducluzeau, Z Benhadji- Zouaoui and J Delaunay
CNRS UA 1171, Faculte de Medecine Grange-Blanche, Lyon, France.
We report on spectrin Oran (alpha II/21), a new spectrin variant found in
an Algerian family. It was characterized by the absence of the spots that
classically correspond to the alpha II domain using two- dimensional
analysis of spectrin limit digests. On the contrary, the abnormal domain
was represented by a new set of spots in the 21-Kd and 16-Kd regions, as
demonstrated by Western blots using anti-alpha II domain polyclonal
antibodies. Spectrin Oran (alpha II/21) was found in the homozygous state
in two children belonging to two separate branches of the family. It yields
a severe elliptocytosis. Spectrin self- association was altered. The
variant was much more difficult to prove in the heterozygous state, in
which it results in no clinical and virtually no morphological symptom. In
all four parents involved, however, electrophoretic analysis and Western
blots showed the existence of the alpha II 21-Kd and 16-Kd peptides. In one
parent, who combines spectrin Oran (alpha II/21) and the alpha II type-2
polymorphism, the two-dimensional spots (52, 39, 34, and 29 Kd) were
quantified and appeared reduced by 30%: there was an intermediary decrease
of spectrin self-association in this person. In the three other parents,
spectrin Oran combined with the alpha II type-1 polymorphism. The alpha II
type-1 spots (46, 35, 30, and 25 Kd) appeared in normal range, and spectrin
self-association was normal. Along with previous observations, the present
data emphasize the large fluctuations of the alpha-variant percentage.
Provided spectrin Oran was present in a sufficient proportion, we found an
associated alteration of the beta II domain (that faces the alpha II domain
in the spectrin dimer): the beta II 65-Kd fragment was reduced and the beta
II 52-Kd fragment was reciprocally increased.
Volume 71,
Issue 4,
pp. 1039-1047,
04/01/1988
Copyright © 1988 by The American Society of Hematology
