OBJECTIVE: To describe a novel dinucleotide deletion in the FRDA gene in two Malaysian siblings with FRDA1.
SETTING: Tertiary referral university hospital setting.
PATIENTS AND METHODS: A previously healthy 10-year-old Malaysian boy, presented with fever, lethargy, headaches, dysarthria, dysphagia, vertigo and ataxia which developed over a one week period. His neurological exam revealed evidence of dysarthria and ataxia, mild generalized weakness and choreoform movements of the tongue and hands. His reflexes were absent and Babinski sign was present bilaterally. A nine-year-old sister was found to have mild ataxia but was otherwise neurologically intact.
RESULTS: Molecular genetic studies demonstrated that both siblings were compound heterozygotes with a GAA expansion on one allele and a novel dinucleotide deletion on the other allele.
CONCLUSIONS: We describe a novel dinucleotide deletion in the first exon of the FRDA gene in two siblings with FRDA1. Additionally this is the first report of FRDA1 occurring in a family of southeast Asian descent, it demonstrates intrafamilial phenotypic variability, and confirms that atypical phenotypes are associated with compound heterozygosity.
METHODS: The PubMed, SAGE, Science Direct, the Cochrane Library and Ovid databases were searched for observational studies before October 2018. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS).
RESULTS: Nine case-control studies involving 4385 lung cancer cases and 4142 controls were included in the analysis. The random-effects model was used to combine results from individual studies. The pooled odds ratio was 0.39 (95% CI: 0.27-0.56). There was no heterogeneity across studies (χ2=2.49, p=0.96, I2=0%).
CONCLUSIONS: Current evidence from the case-control studies suggests that the CYP2A6 whole-gene deletion polymorphism decreases the risk of lung cancer. Further research is needed to identify any potential confounding factors that may impact this association.
METHODS: A total of 50 patients with pathologically confirmed brain tumors (13 LGGs, 20 HGGs, and 17 meningiomas) were enrolled in this study. mtDNA was detected by using polymerase chain reaction (PCR) technique and later confirmed via Sanger DNA sequencing.
RESULTS: Overall, mtDNA was observed in 16 (32%) patients and it was significantly correlated with the type of tumor group and sex, being more common in the HGG group and in male patients.
CONCLUSION: The prevalence of mtDNA in Malaysian glioma and meningioma cases has been described for the first time and it was, indeed, comparable with previously published studies. This study provides initial insights into mtDNA in brain tumor and these findings can serve as new data for the global mitochondrial DNA mutations database.
Methods: A total of 42 patients with congenital heart defects, as confirmed by echocardiography, were recruited. Genetic molecular analysis using a fluorescence in situ hybridization (FISH) technique was conducted as part of routine 22q11.2DS screening, followed by multiplex ligation-dependent probe amplification (MLPA), which serves as a confirmatory test.
Results: Two of the 42 CHD cases (4.76%) indicated the presence of 22q11.2DS, and interestingly, both cases have conotruncal heart defects. In terms of concordance of techniques used, MLPA is superior since it can detect deletions within the 22q11.2 locus and outside of the typically deleted region (TDR) as well as duplications.
Conclusion: The incidence of 22q11.2DS among patients with CHD in the east coast of Malaysia is 0.047. MLPA is a scalable and affordable alternative molecular diagnostic method in the screening of 22q11.2DS and can be routinely applied for the diagnosis of deletion syndromes.