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This variant, also called α-IIa, has been seen frequently in individuals with recessive Hereditary pyropoikilocytosis. This appears to be the result of linkage to α-LEPRA (a C>T substitution at position -99 of intron 30); A970D is later reported as functionally neutral.
Insufficiently evaluated pathogenic
(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)
Summary of published research, and additional commentary
Edited in this revision:
Maillet P, Alloisio N, Morlé L, Delaunay J. Spectrin mutations in hereditary
elliptocytosis and hereditary spherocytosis. Hum Mutat. 1996;8(2):97-107. PubMed
They mention the allele α-LEPRA as also implicated in hereditary spherocytosis, a C>T substitution at position -99 of intron 30. They say this is linked in cis to the α-IIs (A970D) substitution. The α-LEPRA variant appears to be implicated as the causal variant.
Delaunay J, Nouyrigat V, Proust A, Schischmanoff PO, Cynober T, Yvart J,
Gaillard C, Danos O, Tchernia G. Different impacts of alleles alphaLEPRA and
alphaLELY as assessed versus a novel, virtually null allele of the SPTA1 gene in
trans. Br J Haematol. 2004 Oct;127(1):118-22. PubMed PMID: 15384986.
Costa DB, Lozovatsky L, Gallagher PG, Forget BG. A novel splicing mutation of
the alpha-spectrin gene in the original hereditary pyropoikilocytosis kindred.
Blood. 2005 Dec 15;106(13):4367-9. Epub 2005 Sep 8. PubMed PMID: 16150946; PubMed
Central PMCID: PMC1895230.
This variant is noted to be linked to alpha-LEPRA and is seen frequently in individuals with recessive Hereditary pyropoikilocytosis.
hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr1:158624528