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First report of the spectrum of δ‐globin gene mutations in O mani subjects – identification of novel mutations
Author(s) -
Alkindi S.,
AlZadjali S.,
Daar S.,
Ambusaidi R.,
Gravell D.,
Al Haddabi H.,
Krishnamoorthy R.,
Pathare A.
Publication year - 2015
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12272
Subject(s) - compound heterozygosity , mutation , microbiology and biotechnology , genetics , ferritin , gene , gene mutation , loss of heterozygosity , globin , biology , medicine , allele
Summary Introduction Both coinheritance of thalassemic δ‐globin mutation and coexistence of iron deficiency anemia ( IDA ) tend to decrease HbA 2 (α 2 δ 2 ) level and thereby poses a diagnostic conundrum in β‐thalassemia trait. Methods We retrospectively studied 78 O mani subjects, presenting with low HbA 2 level by high‐performance liquid chromatography ( HPLC ), and their DNA was sequenced for the presence of mutations in the δ‐globin gene ( HBD ). In these subjects, their serum ferritin levels allowed evaluation of the degree of iron deficiency. Results Overall, six different δ‐globin gene mutations were observed in 40 study subjects (51.3%) and IDA in 33 subjects, with the remaining five subjects showing normal HBD sequence and serum ferritin level. Among the subjects with δ‐globin gene mutations, seven had an associated IDA confirmed by significantly low serum ferritin levels. Heterozygosity for the delta (+) cd27G‐‐>T mutation (HbA 2 ‐Yialousa; HBD : c.82G>T) was the most common abnormality observed ( n = 26, 66.6%) followed by heterozygosity for HBD c.‐118C‐>T (d ‐68 C‐>T) ( n = 6, 15.4%), for cd16G‐‐>C ( n = 4, 10.3%), for cd98G‐‐>A ( n = 2, 5.1%), for cd142G‐‐>C ( n = 1, 2.6%), and for cd147G‐‐>T ( n = 1, 2.6%). Conclusions These delta mutations exhibit low HbA 2 either due to a shift in the HPLC position or due to their bona fide thalassemic feature. Two mutations, namely cd142 G‐‐>C ( GCC to CCC , Ala to Pro) and stop codon cd147 G‐‐>T (stop to Leu with elongation of 15 amino acids), herein first reported are novel. Coexistence of IDA could lead to erroneous diagnostic interpretation unless it is specifically looked for.