Gene Mutation Spectrum among Alpha-Thalassaemia Patients in Northeast Peninsular Malaysia

(1) Background: Alpha (alpha)-thalassaemia is a genetic disorder that affects 5% of the world population. Deletional or nondeletional mutations of one or both HBA1 and HBA2 on chromosome 16 will result in reduced production of alpha-globin chains, a component of haemoglobin (Hb) that is required for the formation of red blood cells (RBCs). This study aimed to determine the prevalence, haematological and molecular characterisations of alpha-thalassaemia. (2) Method: The parameters were based on full blood count, high-performance liquid chromatography and capillary electrophoresis. The molecular analysis involved gap-polymerase chain reaction (PCR), multiplex amplification refractory mutation system-PCR, multiplex ligation-dependent probe amplification and Sanger sequencing. (3) Results: With a total cohort of 131 patients, the prevalence of alpha-thalassaemia was 48.9%, leaving the remaining 51.1% with potentially undetected alpha gene mutations. The following genotypes were detected: -alpha(3.7)/alpha alpha (15.4%), -alpha(4.2)/alpha alpha (3.7%), --(SEA)/alpha alpha (7.4%), alpha(CS)alpha/alpha alpha (10.3%), alpha(Adana)alpha/alpha alpha (0.7%), alpha(Quong Sze alpha)/alpha alpha (1.5%), -alpha(3.7)/-alpha(3.7) (0.7%), alpha(CS)alpha/alpha(CS)alpha (0.7%), -alpha(4.2)/alpha(CS)alpha (0.7%), -(SEA)/alpha(CS)alpha (1.5%), -(SEA)/alpha(Quong Sze)alpha (0.7%), -alpha(3.7)/alpha(Adana)alpha (0.7%), --(SEA)/-alpha(3.7) (2.2%) and alpha(CS)alpha/alpha(Adana)alpha (0.7%). Indicators such as Hb (p = 0.022), mean corpuscular volume (p = 0.009), mean corpuscular haemoglobin (p = 0.017), RBC (p = 0.038) and haematocrit (p = 0.058) showed significant changes among patients with deletional mutations, but not between patients with nondeletional mutations. (4) Conclusions: A wide range of haematological parameters was observed among patients, including those with the same genotype. Thus, a combination of molecular technologies and haematological parameters is necessary for the accurate detection of alpha-globin chain mutations.

Automated summary

This study aimed to determine the prevalence, haematological and molecular characterisations of alpha-thalassaemia. With a total cohort of 131 patients, the prevalence of alpha-thalassaemia was 48.9%, leaving the remaining 51.1% with potentially undetected alpha gene mutations. Haematological parameters showed significant changes among patients with deletional mutations, but not between patients with nondeletional mutations.