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Unstable haemoglobin causing haemolytic anaemia: de novo mutation in Sweden identified by PCR
Author(s) -
LANDIN B.,
ÅSTROM M.
Publication year - 1993
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.1993.tb00992.x
Subject(s) - isoelectric focusing , medicine , loss of heterozygosity , gene , genetics , compound heterozygosity , polymerase chain reaction , mutation , microbiology and biotechnology , allele , biology , enzyme , biochemistry
. A 38‐year‐old Swedish woman was investigated because of mild anaemia resistant to iron therapy. Mild haemolytic disease was found by routine blood tests. Neither HPLC (HbA 1c quantification) nor Hb‐electrofocusing revealed any major abnormal fraction, although in vitro testing of haemoglobin instability indicated the presence of unstable haemoglobin. PCR was used to amplify coding regions of the β globin gene. Direct nucleotide sequencing of this material revealed heterozygosity for a substitution corresponding to the haemoglobin variant α 2 β 2 135(H13)Ala→Pro. This clearly unstable variant, named Hb Altdorf, has earlier been described only in a family of Italian descent. Examination of β globin genes from six family members of the proposita by PCR followed by specific cleavage with the restriction enzyme Ban I, revealed the mutation in her two children but not in her parents or siblings. This case demonstrates that haemoglobin variants can not be ruled out as a cause of haematological disease even if the parents lack symptoms and standard tests, such as HPLC and electrophoresis/electrofocusing, do not reveal major abnormalities.