FIRST STUDY OF THE F508del MUTATION IN MALAYSIAN CHILDREN DIAGNOSED WITH CYSTIC FIBROSIS

Abstract

20 September 2010 Dear Editor, Cystic fibrosis (CF) is the commonest inheritable disease in the Caucasian population with 1 out of 25 people being carriers of a genetic mutation, and the incidence of CF being 1 out of 2500.1 The reported prevalence of CF in migrant children of Asian descent is reported to be 1 in 10 000–31 000, with a greater incidence among Pakistani, Sri Lankan and Indian.2, 3 University of Malaya Medical Center (UMMC) is a tertiary referral hospital, and over a period of 9 years, 12 children were diagnosed with CF. We would like to present the clinical profile and frequency of the F508del mutation in our children with CF. This is an observational, retrospective case note review. Twelve children were diagnosed with CF between 1st February 2000 and 30th June 2009 based on accepted guidelines for the diagnosis of CF.4 Blood for mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene were taken from 11 patients with consent obtained from their parents. Mutation analysis was performed on seven patients using the amplification refractory mutation system technique with published primers for the F508del mutation.5 Four other patients had their DNA analysed overseas in the National Referral Laboratory, Women's and Children's Hospital in Adelaide for the 12 most common CFTR mutations in South Australia, and these are marked in Table 1. The F508del mutation was detected in 3 out of 11 children. Two were Malaysians of south Indian descent, and one was a Yemeni national. Two patients were homozygous for the F508del mutation (one Malaysian Indian and one Yemeni), the other had the F508del only on one allele, and the other mutation was not identified. The only other gene mutation detected was R553X (Malay-Chinese patient), which was detected only on one allele, and another had 7T polymorphism detected on both alleles (unknown parentage). The F508del mutation was detected in Malaysian children (excluding the Yemeni and one Malaysian family that refused genetic testing) with a prevalence of 15% (3 out of 20), and our overall mutation yield was 20% (4 out of 20). Our finding is comparable with studies done in India, whereby the F508del gene mutation was present in 19% of their children.3 None of our patients of Chinese or Malay descent had the F508del mutation. The reliance on CF genotype panels from non-Asian (mostly Caucasian) countries does seem to have a low probability of detecting mutations unique to the heterogeneous Asian population, as seen by the four patients. The large number of mutations (more than 1500) and complex gene–gene interactions pose a significant hurdle. Hence, the relevance of genetic testing for CF may be questioned in light of limited resources and many competing needs in developing countries in Asia.6 There is a need to identify the molecular epidemiology of Asian CF patients to assist in genetic counselling and prenatal diagnosis, identification of atypical or mild CF cases and a possible strategy for newborn screening using common CFTR mutations in the Asian population. We would like to thank Dr Janice Fletcher and Mr Paul Nelson from the National Referral Laboratory, Women's and Children's Hospital, Adelaide, South Australia and Dr Zilfalil Alwi, Director of the Human Genome Centre, University Sains Malaysia, Kota Bahru, Malaysia, who helped in the mutation analysis of the CFTR gene of some of our patients.