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Genetic basis of persistent red blood cell microcytosis in the Chinese unexplained by phenotypical testing
  1. Chi-Chiu So1,
  2. Ada K Liu2,
  3. Mandy H Tsang2,
  4. Donna Y Ngai2,
  5. Kin-Sang Leung2,
  6. Amy Y Chan3
  1. 1Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
  2. 2Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Hong Kong, Hong Kong
  3. 3Department of Pathology, Queen Elizabeth Hospital, Hong Kong, Hong Kong
  1. Correspondence to Dr Chi-Chiu So, Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong; scc{at}pathology.hku.hk

Abstract

Aims Hypochromic microcytic anaemia is the hallmark phenotype of thalassaemia. Current phenotypical tests do not provide a diagnosis in a small proportion of patients with red blood cell microcytosis. We aim to evaluate the genetic basis of red cell microcytosis in these cases in our Chinese population.

Methods We identified from a large cohort of 1684 unselected requests for thalassaemia testing 23 Chinese subjects who had unexplained microcytosis after phenotypical iron and haemoglobin studies. In 18 of these subjects with available DNA, extensive genotypical analysis of the α and β globin gene cluster was performed, including gap-PCR, multiplex amplification-refractory mutation system, Sanger sequencing and multiplex ligation-dependent probe amplification.

Results Occult single and double α globin gene (HBA1, HBA2) deletions and α thalassaemic haemoglobinopathies (Haemoglobin Quong Sze, Haemoglobin Constant Spring) were the genetic basis for the microcytosis. Occult β globin gene (HBB) mutations and δ globin gene (HBD) abnormalities masking β thalassaemia are not seen.

Conclusions A cost-effective genotyping approach for the detection of these occult globin gene mutations can be proposed. The identification of these mutations is important for making a diagnosis and for the provision of accurate genetic counselling. (This paper adds to our understanding of the genetic basis of red blood cell microcytosis in clinical practice, and it provides a cost-effective approach for genotyping in diagnostic laboratories).

  • THALASSAEMIA
  • GENETICS
  • DIAGNOSTICS

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