Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

Abstract

HBA2We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia

“…Our data reported herein is also in agreement with previous reports regarding the Hb Adana cases in Indonesia (Nainggolan et al, 2010;Nainggolan et al, 2013;Megawati et al, 2014). Both Malaysia and Indonesia are culturally related neighbors located in the same region.…”

Hb Adana (HBA2 or HBA1: c.179G > A) and alpha thalassemia: Genotype–phenotype correlation

“…The remainder of Adana cases compounded with alpha globin deletions yielded varying phenotypes, ranging from mild anemia (−α 3.7 and −α 4.2 ) to severe HbH‐like disease (− − 20.5 and −α 4.2‐QT [Q‐Thailand]) . The cases of Adana alpha 2 mutations that combined with a single alpha 2 nondeletional mutation in general gave more severe HbH‐like presentations (α2 CS [Constant Spring], α2 Paksé , α2 IVS‐II‐142 , α2 IVS‐I‐1 , α2 codon24 , α2 codon22 , and rSNP 149709T > C) . The incidence of hydrops fetalis was generally associated with genotype and not ethnicity.…”

“…11,19,37,38 The cases of Adana alpha 2 mutations that combined with a single alpha 2 nondeletional mutation in general gave more severe HbH-like presentations ( 2 CS [Constant Spring], 2 Paksé , 2 IVS-II-142 , 2 IVS-I-1 , 2 codon24 , 2 codon22 , and rSNP 149709T > C). 15,17,22,35,36,39,40 The incidence of hydrops fetalis was generally associated with genotype and not ethnicity. Mild differences in clinical severity between patients of identical genotype were likely due to various unknown genetic factors implicated in HbH disease that require further study.…”

Clinical and Haematological Parameters of Commonly Reported Non-deletional α-thalassaemia Mutations in Southeast Asia: A Review

“…mutation (c.2delT), codon 30 (c.91_93delGAG), Hb CS (c.427T>C), Hb QS (c.377T>C), Hb Adana (c.179G>A) and Hb Evora (c.106T>C) (11,12). Although nondeletional mutations are less common than deletional ones, they may show more severe clinical phenotypes because they are associated with protein stability (13).…”