1.Single mitochondrial DNA deletions in chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) patients from a multiethnic Asian population
Jia-Woei Chong ; Azlina Ahmad Annuar ; Kum-Thong Wong ; Meow-Keong Thong ; Khean-Jin Goh
Neurology Asia 2014;19(1):27-36
Mitochondrial DNA (mtDNA) deletions are a major cause of chronic progressive external ophthalmoplegia
(CPEO) and Kearns-Sayre syndrome (KSS). We analyzed single mtDNA deletions in 11 CPEO and
one KSS patients by means of Southern blot and long polymerase chain reaction (PCR) assays. The
deletion sizes ranged from 3.4 kb to 6.9 kb whereas the heteroplasmy level varied from 18.8% to
85.5%. Two unique deletions sized 4320 bp and 4717 bp were found. This study represents the first
genetic screen of mtDNA disorders in Malaysia, and it follows the data seen in other published reports
on CPEO and KSS genetic aetiology.
2.The frequency of common mitochondrial DNA mutations in a cohort of Malaysian patients with specifi c mitochondrial encephalomyopathy syndromes
Jia-Woei Chong ; Azlina Ahmad Annuar ; Kum-Thong Wong ; MeowKeong Thong ; Khean-Jin Goh
Neurology Asia 2011;16(4):321-327
A cohort of Malaysian patients with clinico-pathological diagnosis of three specifi c mitochondrial
encephalomyopathy syndromes comprising of mitochondrial encephalomyopathy, lactic acidosis
and stroke-like episodes (MELAS), myoclonus epilepsy with ragged-red fi bers (MERRF) and Leigh
syndrome were studied to determine the frequency of their common mitochondrial DNA mutations. The
‘hot-spot’ point mutations for MELAS, MERRF and Leigh syndrome were screened. In the absence
of common point mutations, screening of large-scale deletions as well as sequencing of tRNALeu and
tRNALys genes were performed. Of 22 patients studied, nine m.3243A>G mutations, four m.8344A>G
mutations, one m.8993T>G mutation and one deletion were identifi ed (65% detection rate). While the
m.3243A>G mutation was closely associated with MELAS, the m.8344A>G was more heterogenous,
being seen in one MERFF, two isolated mitochondrial myopathies and one Leigh syndrome patient.
Screening for m.8993T>G in Leigh syndrome has a low yield as unsurprisingly Leigh syndrome has
considerable genetic heterogeneity.
3.Purposeless Groaning in Parkinson's Disease
Shen Yang LIM ; Ai Huey TAN ; Jia Lun LIM ; Azlina AHMAD-ANNUAR
Journal of Movement Disorders 2018;11(2):87-88
Purposeless groaning has been reported in advanced progressive supranuclear palsy. We present a case of purposeless groaning occurring as a primary complaint in a patient with advanced Parkinson's disease. Purposeless groaning is thought to be a manifestation of disinhibition and perseveration due to frontal-subcortical dysfunction. Proper recognition of this phenomenon will help clinicians to avoid unnecessary investigations and treatment (e.g., prescription of opioid medications).
Humans
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Parkinson Disease
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Prescriptions
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Supranuclear Palsy, Progressive
4.Glucocerebrosidase genetic variants in Malays with early and late-onset Parkinson’s disease
Nur Fadhlina Mohamad Pakarulrazy ; Saiful Effendi Syafruddin ; Nurul Syakima Ab Mutalib ; Azlina Ahmad Annuar ; Shen-Yang Lim ; Rahman Jamal ; Nor Azian Abdul Murad ; Norlinah Mohamed Ibrahim
Neurology Asia 2020;25(1):39-46
Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing
Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among
Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA
mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients.
Methods:EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM System.
Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G,p.S146L,
p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A
and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition,
c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed
GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence
of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were
not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD
vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715].
Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might
predict the increase susceptibility of Malays to develop PD at young age. These findings could add
knowledge into the existing evidences linking genetic alterations in GBA and PD.
5.Dystrophin gene analysis in Duchenne/Becker dystrophy in a Malaysian population using multiplex polymerase chain reaction
Jin-Ai Mary Anne Tan ; James Hsian-Meng Chan B ; Kim-Lian Tan ; Azlina Ahmad Annuar ; Moon-Keen Lee ; Khean-Jin Goh ; Kum-Thong Wong
Neurology Asia 2010;15(1):19-25
Dystrophinopathy is the commonest form of muscular dystrophy and comprises clinically recognized
forms, Duchenne dystrophy and Becker dystrophy. Mutations in the dystrophin gene which consist of
large gene deletions (65%), duplications (5%) and point mutations (30%) are responsible for reducing
the amount of functional dystrophin protein in skeletal muscle fi bres leading to fi bre destruction and
disease. The aims of this study are to investigate the detection rate, types and distribution of large
gene deletions in Malaysian dystrophinopathy patients using the multiplex polymerase chain reaction
(MPCR). MPCR of 18 “hot-spot deletion” regions along the dystrophin gene was performed on DNA
from 48 muscle biopsy-confi rmed cases of dystrophinopathy. A positive detection rate of 58% (28/48)
was observed, where 84% (16/19) Indian, 35% (6/17) Chinese and 50% (6/12) Malay ethnic groups
showed deletions in their dystrophin genes. The Malaysian Indians appear to have a higher prevalence
for large gene deletions compared to the Chinese and Malays. Further analyses of 42 confi rmed
positive cases (present 28 plus previous 14 cases) by MPCR showed the majority of deletions were
in the mid-distal region of the dystrophin gene (81% in exons 45-60). The MPCR is a specifi c and
sensitive method for confi rmation of gene deletions responsible for dystrophinopathy.
6.Exercise induced cramps and myoglobinuria in dystrophinopathy – a report of three Malaysian patients
Azlina Ahmad Annuar ; Kum Thong Wong ; Ai Sze Ching ; Meow Keong Thong ; Sau Wei Wong ; Feizel Alsiddiq ; Lai Choo Ong ; Khean Jin Goh
Neurology Asia 2010;15(2):125-131
Dystrophinopathies commonly present as Duchenne or Becker muscular dystrophy but rare, unusual
phenotypes have also been described. We have identifi ed three Malaysian boys with an unusual form
of dystrophinopathy, presenting with exercise-induced cramps and myoglobinuria, but with no apparent
muscle weakness. Immunohistochemistry for dystrophin and genetic analysis confi rmed the diagnosis.
The frequency of this phenotype is unknown but there have been several case reports. Consistent with
these reports, we also found that two of our patients had deletions in the rod domain of dystrophin,
which has been suggested to be associated with this unusual manifestation
8.A Patient with Beta-Propeller Protein-Associated Neurodegeneration: Treatment with Iron Chelation Therapy
Shen Yang LIM ; Ai Huey TAN ; Azlina AHMAD-ANNUAR ; Susanne A SCHNEIDER ; Ping Chong BEE ; Jia Lun LIM ; Norlisah RAMLI ; Mohamad Imran IDRIS
Journal of Movement Disorders 2018;11(2):89-92
We present a case of beta-propeller protein-associated neurodegeneration, a form of neurodegeneration with brain iron accumulation. The patient harbored a novel mutation in the WDR45 gene. A detailed video and description of her clinical condition are provided. Her movement disorder phenomenology was characterized primarily by limb stereotypies and gait dyspraxia. The patient's disability was advanced by the time iron-chelating therapy with deferiprone was initiated, and no clinical response in terms of cognitive function, behavior, speech, or movements were observed after one year of treatment.
Brain
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Chelation Therapy
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Cognition
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Extremities
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Gait Apraxia
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Humans
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Iron
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Movement Disorders
9.Lack of association between the LRRK2 A419V variant and Asian Parkinson's disease.
Aroma Agape GOPALAI ; Shen Yang LIM ; Zariah Abdul AZIZ ; Soo Kun LIM ; Li Ping TAN ; Yip Boon CHONG ; Chong Tin TAN ; Santhi PUVANARAJAH ; Shanti VISWANATHAN ; Rishikesan KUPPUSAMY ; Ai Huey TAN ; Thien Thien LIM ; Gaik Bee EOW ; Mohamed Ibrahim NORLINAH ; Hui Hua LI ; Yi ZHAO ; Azlina AHMAD-ANNUAR
Annals of the Academy of Medicine, Singapore 2013;42(5):237-240
INTRODUCTIONThe G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.
MATERIALS AND METHODSEight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.
RESULTSThe heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).
CONCLUSIONA419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alanine ; genetics ; Case-Control Studies ; China ; ethnology ; Cohort Studies ; Cytosine ; Female ; Gene Frequency ; Genetic Variation ; genetics ; Genotype ; Heterozygote ; Humans ; India ; ethnology ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Malaysia ; ethnology ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Polymorphism, Genetic ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors ; Singapore ; Thymine ; Valine ; genetics ; Young Adult
10.Alternating Hemiplegia of Childhood in a Person of Malay Ethnicity with Diffusion Tensor Imaging Abnormalities
Ai Huey TAN ; Tien Lee ONG ; Norlisah RAMLI ; Li Kuo TAN ; Jia Lun LIM ; Mohamad Addin AZHAN ; Azlina AHMAD-ANNUAR ; Khairul Azmi IBRAHIM ; Zariah ABDUL-AZIZ ; Laurie J OZELIUS ; Allison BRASHEAR ; Shen Yang LIM
Journal of Movement Disorders 2019;12(2):132-134
No abstract available.
Diffusion Tensor Imaging
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Diffusion
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Hemiplegia
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Humans