Detection of beta-globin gene mutations among Kelantan Malay thalassaemia patients by polymerase chain reaction restriction fragment length polymorphism.

INTRODUCTION: Beta-thalassaemia major is an autosomal recessive disorder that results in severe microcytic, hypochromic, haemolytic anaemia among affected patients. Beta-thalassaemia has emerged as one of the most common public health problems in Malaysia, particularly among Malaysian Chinese and Malays. This study aimed to observe the spectrum of mutations found in Kelantan Malay beta-thalassaemia major patients who attended the Paediatrics Daycare Unit, Hospital Universiti Sains Malaysia, Kelantan, Malaysia, the data of which was being used in establishing the prenatal diagnosis in this Human Genome Centre. METHODS: This was a cross-sectional study conducted with 35 Kelantan Malay beta-thalassaemia major patients. DNA was extracted from the blood collected from the patients and subjected to polymerase chain reaction (PCR) amplification. Six restriction enzymes were used to digest the PCR products for the detection of mutations. RESULTS: Five out of the six beta-globin gene defects were detected, namely, IVS-1 nt5 (G>C), IVS-1 nt1 (G>T), codon 26 (G>A), codon 41-42 (4 bp del) and codon 19 (A>G). The mutation which was not observed in this study was in codon 15 (G>A). The two most common mutations observed were codon 26 (G>A) and IVS-1 nt5 (G>C), which was detected in 26 and 17 patients, respectively. Two patients did not show any of the six mutations. CONCLUSION: Our results added to the existing data on the common beta-globin gene defects in Kelantan Malay beta-thalassaemia patients.

Cytogenetic and clinical profile of Down syndrome in Northeast Malaysia.

INTRODUCTION: This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome in Malaysia. METHODS: Retrospective analysis was performed on the case records of 149 patients confirmed as Down syndrome by cytogenetic analysis at Human Genome Centre and Genetic Clinic at the Universiti Sains Malaysia. RESULTS: Among the 149 cases of Down syndrome presenting over a period of 4.2 years, free trisomy (non-disjunction) was present in 141 cases (94.6 percent). One case (0.7 percent) had translocation, and seven cases (4.7 percent) were mosaics. Average age at presentation was 10.6 months. Average maternal age at birth of the affected child was 32.3 years. The prominent craniofacial features noted were upslanting palpebral fissures (89.3 percent), flat facial profile (64.9 percent), low set ears (56.1 percent), epicanthic folds (17.5 percent) and protruding tongue (19.2 percent). A total of 52.6 percent of the cases had documented hypotonia. Characteristic limb and dermatoglyphic anomalies included short stubby fingers (24.5 percent), sandal gap (33.3 percent), unilateral or bilateral simian crease (36.8 percent) and clinodactyly (19.2 percent). Ophthalmological abnormalities, such as hypertelorism, were presented in 33.3 percent of the cases. Congenital heart disease was diagnosed in 35 out of 71 cases (49.3 percent) and gastrointestinal anomalies were noted in 18 out of 79 cases (22.7 percent) analysed. CONCLUSION: Efforts to establish early diagnosis and a proper screening for high association with systemic anomalies should be undertaken among the Down syndrome patients in this population.