METHODS: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.
RESULTS: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.
CONCLUSIONS: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.
MATERIALS AND METHODS: This is prospective controlled trial. Peripheral venous blood sample is obtained from 20 patients with AAA and 36 normal control subjects. MMP-9 concentration levels were determined by an enzyme-linked immunosorbent assay and compared with subjects abdominal ultrasonography or computed tomography of abdomen.
RESULTS: Mean (± SE) MMP-9 was 23.94 ± 0.60 ng/mL in normal control subjects and 21.39 ± 1.03 ng/mL in patients with AAAs (p ← 0.05 versus normal control subjects). MMP-9 correlate significantly with AAA (p=0.004). There was no correlation of MMP-9 levels with age, gender, or other risk factors. The cutoff point is 12.54 for aorta size <3.0 cm. The sensitivity and specificity of MMP-9 were 60% and 64% respectively.
CONCLUSIONS: MMP-9 levels correlate significantly with AAA with a cutoff point of 12.54. However, the utility of MMP-9 as a diagnostic test is limited due to low sensitivity and specificity. An elevated MMP-9 has limited use to predict the presence of AAA (positive predictive value: 60%) and a normal MMP-9 level was insufficient to determine the absence of AAA (negative predictive value: 36.1%).