PINK1 p.Leu347Pro mutations in Malays: Prevalence and illustrative cases.

BACKGROUND: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited. 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.

Challenges in the management of massive intraorbital and hemifacial arteriovenous malformation as causing life-threatening epistaxis.

Arteriovenous malformations are congenital lesions that may evolve with time and manifest in a plethora of presentations. They can occur as torrential epistaxis when it extensively involves the facial region. Multi-imaging modalities are available to assist in characterizing the structure of the lesion as well as its location and extent. This complex disease requires a multidisciplinary team approach with preoperative embolization and surgery. We present a rare cause of life-threatening epistaxis in a gentleman with a longstanding orbital and hemifacial arteriovenous malformation and discuss the complexities involved in its management.

Comparison study of growth plate fusion using MRI versus plain radiographs as used in age determination for exclusion of overaged football players.

BACKGROUND: MRI of distal radius fusion is currently being used in the U17 World Cup to exclude overaged players. Developing countries that cannot afford to perform MRI on their players are using plain radiographs based on the same MRI criteria of fusion. OBJECTIVE: The aim of this study is to compare the grade of fusion of the left wrist distal radial growth plate between MRI and plain radiographs. METHODS: 150 healthy male football players were grouped into five age groups ranging from 15 to 19 years old. Each participant had coronal T1-weighted MRI and plain radiograph of the left wrist. The degree of distal radius fusion was rated randomly by three radiologists using a six-stage grading system proposed by the FIFA Research Centre. RESULTS: MRI assessment of distal radial growth plate fusion has good correlation with plain radiograph fusion (r=0.949). The mean of x-ray grading is higher than the MRI grading in the 15, 16, 17, 18 and 19 years old age groups with p=0.443, 0.001, 0.009, <0.001 and 0.003, respectively, using Wilcoxon signed ranked test. Intraobserver and interobserver correlations were high (r=0.9). T1 MRI correlation with chronological age (r=0.771) was close to plain radiographs (r=0.821) with p value of <0.001. CONCLUSION: This article is of major importance as it is the first to show that x-rays significantly overrate the grading of fusion in this age group and therefore should not be used to exclude overaged players as is occurring now to the distress of many genuinely eligible players.

Bilateral temporal bone xanthoma. Case report.

Xanthoma formation is frequently seen over the subcutaneous tissue of extensor surfaces and tendons that have received minor trauma or friction in patients with hypercholesterolemia. However, temporal bone xanthomas with intracranial extension are uncommon. To the best of the authors' knowledge, this is the second report in the literature in which bilateral extension of a xanthoma is described. Xanthomas of the temporal bone are benign lesions, and complete or even partial removal is effective. The predisposing cause of the lesion should also be treated.