Enabling routine β-thalassemia Prevention and Patient Management by scalable, combined Thalassemia and Hemochromatosis Mutation Analysis

Ghazala Hashmi, Asim Qidwai, Kristopher Fernandez, Michael Seul, Ghazala Hashmi, Asim Qidwai, Kristopher Fernandez, Michael Seul

Abstract

Background: Beta (β)-thalassemia is one of the most common inherited disorders worldwide, with high prevalence in the Mediterranean, the Middle East and South Asia. Over the past 40 years, awareness and prevention campaigns in many countries have greatly reduced the incidence of affected child births. In contrast, much remains to be done in South-Asia. Thus, for Pakistan, an estimated ~ 7000 children annually are born with thalassemia, with no sign of improvement. Although there is good agreement that intermarriage of carriers significantly contributes to the high prevalence of the disorder, effective tools for molecular screening and diagnosis on which to base prevention programs are not readily available.

Methods: Here, we present results for a novel LeanSequencing™ process to identify a combination of 18 β-thalassemia mutations (including the sickle cell anemia mutation, HbS, and structural variants HbC and HbE) and 2 hemochromatosis mutations in a multi-ethnic population of 274 pediatric and adolescent patients treated at Afzaal Memorial Thalassemia Foundation in Karachi, Pakistan.

Results: We found substantial differences in the predominance of disease-causing mutations among the principal ethnic groups in our cohort. We also found the hemochromatosis mutation H63D C > G in 61 (or 22.1%) of our patients including 6 (or 2.2%) homozygotes.

Conclusions: To our knowledge, this is the first screen combining a large set of β-thalassemia and hemochromatosis mutations, so as to facilitate the early identification of patients who may be at increased potential risk for complications from iron overload and thereby to improve the prospective management of thalassemia patients.

Keywords: Beta (β)-thalassemia; Hemochromatosis; Inherited disorders; Iron overload; LeanSequencing; Patient management; Prevention.

Conflict of interest statement

Authors GH, KF and MS are employees of BioMolecular Analytics, LLC. AQ is an employee of Afzaal Memorial Thalassemia Foundation Hospital and is one of the treating physicians for the patients.

Figures

Fig. 1
Fig. 1
Lean Sequencing Process Flow
Fig. 2
Fig. 2
Mutation Frequencies in the Most Prevalent Ethnic Groups In Our Cohort. Top: Locally predominant mutations; Bottom: Less abundant mutations; none of these were observed in Balochi patients (not shown)
Fig. 3
Fig. 3
H63D variant allele frequency for principal ethnicities in our patient cohort

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Source: PubMed

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