title: Multiplex amplification refractory mutation system (MARMS) for the detection of β-globin gene mutations among the transfusion-dependent β-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia.
abstract: The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Sarifah
authors.initials: S
authors.lastname: Hanafi
authors.affiliation: Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Rosline
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Rosnah
authors.initials: R
authors.lastname: Bahar
authors.affiliation: Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Wan Zaidah
authors.initials: WZ
authors.lastname: Abdullah
authors.affiliation: Department of Hematology, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Muhammad Farid
authors.initials: MF
authors.lastname: Johan
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Noor Diana
authors.initials: ND
authors.lastname: Rashid
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Nurul Fatihah
authors.initials: NF
authors.lastname: Azman
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Ariffin
authors.initials: A
authors.lastname: Nasir
authors.affiliation: Hematology Unit, Cancer Research Centre, Institute for Medical Research Kuala Lumpur.
authors.forename: Syahzuwan
authors.initials: S
authors.lastname: Hassan
authors.affiliation: Hematology Unit, Cancer Research Centre, Institute for Medical Research Kuala Lumpur.
authors.forename: Rahimah
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Azizah
authors.initials: A
authors.lastname: Othman
authors.affiliation: Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Mohd Ismail
authors.initials: MI
authors.lastname: Ibrahim
authors.affiliation: Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Surianti
authors.initials: S
authors.lastname: Sukeri
authors.affiliation: Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Sarina
authors.initials: S
authors.lastname: Sulong
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Surini
authors.initials: S
authors.lastname: Yusoff
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Nor Sarwany
authors.initials: NS
authors.lastname: Mohamad
authors.affiliation: Department of Ophthalmology, Universiti Sains Malaysia Malaysia.
authors.forename: Adil
authors.initials: A
authors.lastname: Hussein
authors.affiliation: School of Dental, Universiti Sains Malaysia Malaysia.
authors.forename: Rozita
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Regenerative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia Malaysia.
authors.forename: Narazah
authors.initials: N
authors.lastname: Yusoff
authors.affiliation: Regenerative Medicine Cluster, Advanced Medical & Dental Institute, Universiti Sains Malaysia Malaysia.
authors.forename: Badrul Hisyam
authors.initials: BH
authors.lastname: Yahaya
authors.affiliation: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Malaysia.
authors.forename: Endom
authors.initials: E
authors.lastname: Ismail
authors.affiliation: Department of Pediatrics, Hospital Raja Perempuan Zainab II Kota Bharu Kelantan, Malaysia.
authors.forename: Nik Khairuddin Nik
authors.initials: NK
authors.lastname: Yussof
authors.affiliation: Department of Medical, Hospital Kuala Krai Kelantan, Malaysia.
authors.forename: Sinari
authors.initials: S
authors.lastname: Salleh
authors.affiliation: Department of Pediatrics, School of Medical Sciences, Universiti Sains Malaysia Malaysia.
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
keywords: MARMS-PCR; Malay; mutation; thalassemia; β-globin gene