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  1. Tan JSJ, Ong KC, Ong DBL, Wu YS, Razack A, Kuppusamy S, et al.
    Malays J Pathol, 2019 Dec;41(3):243-251.
    PMID: 31901908
    INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene.

    MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.

    RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent.

    CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

    Matched MeSH terms: Trinucleotide Repeats/genetics
  2. Salehi MH, Houshmand M, Aryani O, Kamalidehghan B, Khalili E
    Iran Biomed J, 2014;18(1):28-33.
    PMID: 24375160
    BACKGROUND: Friedreich ataxia (FRDA) is an autosomal recessive disorder caused by guanine-adenine-adenine (GAA) triplet expansions in the FXN gene. Its product, frataxin, which severely reduces in FRDA patients, leads to oxidative damage in mitochondria. The purpose of this study was to evaluate the triple nucleotide repeated expansions in Iranian FRDA patients and to elucidate distinguishable FRDA clinical differences in these patients.

    METHODS: A number of 22 Iranian patients (8 females and 14 males) from 16 unrelated families were studied. DNA was extracted from the peripheral blood of patients. The frequency and length of (GAA)n repeats in intron 1 of the FXN gene were analyzed using long-range PCR. In this study, the clinical criteria of FRDA in our patients and the variability in their clinical signs were also demonstrated.

    RESULTS: An inverse relationship was observed between GAA repeat size and the age of onset. Although some distinguishable clinical features (such as limb ataxia and lower limb areflexia) were found in our patients, 90-95% of them had extensor plantar response and dysarthria. The results showed only one positive diabetes patient and also different effects on eye movement abnormality among our patients.

    CONCLUSION: The onset age of symptoms showed a significant inverse correlation with allele size in our patients (P>0.05). Based on comparisons of the clinical data of all patients, clinical presentation of FRDA in Iranian patients did not differ significantly from other FRDA patients previously reported.

    Matched MeSH terms: Trinucleotide Repeats/genetics*
  3. Ambrose KK, Ishak T, Lian LH, Goh KJ, Wong KT, Ahmad-Annuar A, et al.
    BMJ Open, 2017 03 31;7(3):e010711.
    PMID: 28363916 DOI: 10.1136/bmjopen-2015-010711
    OBJECTIVE: The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia.

    DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.

    OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.

    RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.

    CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.

    Matched MeSH terms: Trinucleotide Repeats/genetics*
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