Iswari Setianingsih

Hydrops Fetalis Associated with Homozygosity for Hb Adana [α59(E8)Gly→Asp (α2)]

We describe cases of hydrops fetalis associated with nondeletional α-thalassemia (α-thal), in three unrelated Indonesian families. The genotypes of the fetuses and their parents were generated by DNA sequencing and by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)-based method to rapidly identify mutations detected by sequencing. Two of the fetuses had hydrops fetalis and homozygous α59(E8)Gly→Asp (α2), also known as Hb Adana. The third fetus was also suspected to be homozygous for Hb Adana because both parents were carriers of this mutation. This study shows that homozygosity for Hb Adana is associated with hydrops fetalis in the Indonesian population. We discuss this mutation and its various phenotypes including compound heterozygosity with other α-thal mutations and describe a simple approach to genetic testing that will clarify the risk of hydrops fetalis in the offspring of couples carrying this nondeletional mutation.

Alpha thalassaemia in Indonesia: phenotypes and molecular defects.

Alpha thalassaemia is a hereditary blood disorder characterized by haemolytic anaemia. It is caused by mutations in the α-globin genes which lead to a decrease in or absence of α-globin chain production. Since the α-globin chain is the subunit for both fetal (α2γ2) and adult (α2s2) haemoglobin, homozygous a-thalassaemia can cause anaemia in fetuses and adults. Another hereditary blood disorder, s-thalassaemia, is caused by mutations in the s-globin gene. Together, α-and s-thalassaemia are the most common single gene genetic disorders in humans (Weatherall, 1997). These disorders are primarily found in areas where malaria was and may still be endemic.

Interaction of Hb adana (HBA2: c.179G>A) with deletional and nondeletional α(+)-thalassemia mutations: diverse hematological and clinical features.

We describe 27 cases of mild-to-severe α-thalassemia (α-thal) syndrome caused by interaction of Hb Adana [α59(E8)Gly→Asp, GGC>GAC (α2)] with deletional and nondeletional α+-thal mutations in Indonesian patients. Hematological profiles and clinical manifestations of all patients were assessed by routine procedures. The genotypes were generated by a multiplex-polymerase chain reaction (m-PCR), PCR-RFLP (restriction fragment length polymorphism)-based method, and DNA sequencing. The α-thal patients who had Hb Adana in combination with the 3.7 kb deletion mostly have mild-to-moderate anemia. In contrast, patients who were compound heterozygotes for Hb Adana and nondeletional mutations, generally showed a more severe anemia and it mostly presented in childhood. Thus, accurate diagnosis of α-thal disorders is not only important for future management of these patients but also for providing proper genetic counseling to the family.

Rapid screening for the most common β thalassaemia mutations in south east Asia by PCR based restriction fragment length polymorphism analysis (PCR-RFLP)

Editor—The heterogeneity of the molecular lesions which underlie the failure of erythropoietic cells to synthesise normal haemoglobin in β thalassaemia1 is a complicating factor in its molecular diagnosis. However, although more than 100 different mutations have been identified, mostly single base substitutions or small deletions and insertions in the β globin gene, in many populations the bulk of β thalassaemia is caused by a population specific spectrum of only a small number of mutations.1The strategy for the detection of mutations in patients, therefore, normally involves screening in the first instance for a small number of mutations that are the most common for the population concerned. Two of the most commonly used screening procedures are dot blot or reverse dot blot hybridisation2 and the amplification refractory mutation system (ARMS).3 While these procedures are satisfactory in the hands of the more experienced specialised laboratories, the exacting conditions required for the performance of allele specific hybridisation or PCR amplification steps have made them less reproducible in less advanced laboratories.4 5 In south east Asia, where in some regions the frequency of β thalassaemia can be as high as 10%,6 7 many laboratories in medium sized provincial hospitals and universities are suitably …

Human Genome Diversity and Disease on the Island Southeast Asia

The island Southeast Asia (also referred to in the literature as the Malay, the Southeast Asian, and, more recently, the Indo-Malaysian Archipelago), which includes present-day Indonesia, East Malaysia, and the Philippines, is an area with very diverse populations. Archaeological records indicate that this archipelago has been a dynamic theatre of human development and migration for tens of millenniums, and thus is of great interest in terms of human genome diversity. The Indonesian part of the archipelago alone is home to around 500 ethnic populations, each with distinct cultural and linguistic characteristics, representing vast genome diversity.

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 We 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.

The Hemoglobin O mutation in Indonesia: distribution and phenotypic expression

AbstractWe have investigated hemoglobin O Indonesia (HbOIna) in related ethnic populations of the Indonesian archipelago: 1725 individuals of the five ethnic populations of South Sulawesi (Bugis, Toraja, Makassar, Mandar, and Kajang) and 959 individuals of the neighboring islands, who were divided into five phylogenetic groups: (a) Batak; (b) Malay from Padang, Pakanbaru, and Palembang in the island of Sumatra; (c) Javanese-related populations (Java, Tengger, and Bali) from the islands of Java and Bali; (d) populations of the Lesser Sunda Islands of Lombok, Sumba, and Sumbawa; and (e) the Papuan-language-speaking population of Alor Island. Nineteen individuals heterozygous for HbOIna were identified from the Bugis, Toraja, Makassar, and Kajang ethnic populations, but none from the other populations. In all cases, the underlying mutation was found to be in codon 116 (GAG to AAG) of the α1-globin gene, resulting in the Glu116Lys amino acid change. The level of HbO in the 17 individuals plus 12 additional family members carrying the mutation was found to be 11.6 ± 1.0%, significantly lower than the expected 17%–22%, indicating the instability of HbO.

Iron Absorption in Iron-Deficient Women, Who Received 65 mg Fe with an Indonesian Breakfast, Is Much Better from NaFe(III)EDTA than from Fe(II)SO4, with an Acceptable Increase of Plasma NTBI. A Randomized Clinical Trial

Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO4 or NaFe(III)EDTA with water, revealed that FeSO4 was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency. All subjects received a placebo, 6.5 mg FeSO4, 65 mg FeSO4, 6.5 mg NaFeEDTA, and 65 mg NaFeEDTA with a traditional Indonesian breakfast in one-week intervals. Blood tests were carried out every 60 min for five hours. NTBI detection was performed using the fluorescein-labeled apotransferrin method. Plasma iron values were highly increased after 65 mg NaFeEDTA, twice as high as after FeSO4. A similar pattern was seen for NTBI. After 6.5 mg of NaFeEDTA and FeSO4, NTBI was hardly detectable. NaFeEDTA was highly effective for the treatment of iron deficiency if given with a meal, inhibiting the formation of nonabsorbable Fe-complexes, while NTBI did not exceed the range of normal values for iron-replete subjects.

A commentary on molecular basis of transfusion dependent beta-thalassemia major patients in Sabah

A commentary on molecular basis of transfusion dependent beta-thalassemia major patients in Sabah