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A family with haemolytic anaemia and three β‐globins: the deletion in haemoglobin Atlanta‐Coventry (β75 Leu→Pro, 141 Leu deleted) is not present at the nucleotide level
Author(s) -
George Peter M.,
Myles Timothy,
Williamson David,
Higuchi Russell,
Symmans W. Ashley,
Brennan Stephen O.
Publication year - 1992
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1992.tb08178.x
Subject(s) - nucleotide , atlanta , globin , medicine , genetics , biology , gene , pathology , metropolitan area
Analyses of haemoglobin from a family with an unstable haemoglobin haemolytic anaemia demonstrated that the affected individuals had three β‐globins, namely, normal (β A ), Atlanta (β At ) with a mutation of β75 Leu→Pro, and β‐Atlanta‐Coventry (β At‐Co ) with mutation of β75 Leu→Pro and β141 Leu deleted. These were present in the ratio 66:23:11 respectively. The structure of the β‐globin cluster, however, was found to be normal by Southern blotting: also cytogenetic analysis failed to show any abnormality. DNA sequence analyses demonstrated the presence of the β At mutation in genomic DNA isolated from leucocytes but the Coventry deletion of 141 Leu in β At‐Co was not present in genomic DNA. PCR amplification of the β‐globin cDNA and direct sequencing of the product also failed to demonstrate the Coventry deletion. Thus, it appears that the absence of 141 Leu in the β At‐Co globin is a consequence of the β At mutation in these patients and that both β At and β At‐Co are the product of a single gene. This unusual conclusion is paralleled in the bizarre case of Hb Vicksburg where the deletion of a leucine at β75 is not coded for in genomic DNA.