Identification of novel variants in LRRK2 gene in patients with Parkinson's disease in Serbian population.

BACKGROUND: Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of autosomal dominant Parkinson's disease (PD). Large international studies have revealed that pathogenic mutations are clustered in several exons coding for functional domains of LRRK2 protein, but the mutation frequency differs among populations. Systematic study of LRRK2 mutation prevalence and phenotype in Serbian population has not been performed. METHODS: Comprehensive mutation screening of selected exons of LRRK2 was performed in 486 Serbian PD patients. RESULTS: Previously reported mutations I1371V and G2019S were identified in a single patient each, and c.4536+3A>G substitution in two patients. G2019S is the most common, pathogenic mutation, while pathogenic roles for recurrent variants I1371V and c.4536+3A>G are not confirmed yet. Two novel variants S1508G and I1991V were discovered in 2 unrelated patients. These variants are considered as disease causing according to several software predictions, but additional segregation and functional analyses are required. CONCLUSIONS: Mutation frequency in our study (1.23%) was similar to other European populations, although the most common mutations were underestimated and novel variants were detected. In most cases, symptoms of LRRK2-PD are similar to sporadic PD, so estimation of frequency and penetrance of mutations in different populations is important for efficient genetic testing strategy and counseling.

Quantitative and qualitative gait assessments in Parkinson's disease patients.

BACKGROUND/AIM: Postural impairments and gait disorders in Parkinson's disease (PD) affect limits of stability, impaire postural adjustment, and evoke poor responses to perturbation. In the later stage of the disease, some patients can suffer from episodic features such as freezing of gait (FOG). Objective gait assessment and monitoring progress of the disease can give clinicians and therapist important information about changes in gait pattern and potential gait deviations, in order to prevent concomitant falls. The aim of this study was to propose a method for identification of freezing episodes and gait disturbances in patients with PD. A wireless inertial sensor system can be used to provide follow-up of the treatment effects or progress of the disease. METHODS: The system is simple for mounting a subject, comfortable, simple for installing and recording, reliable and provides high-quality sensor data. A total of 12 patients were recorded and tested. Software calculates various gait parameters that could be estimated. User friendly visual tool provides information about changes in gait characteristics, either in a form of spectrogram or by observing spatiotemporal parameters. Based on these parameters, the algorithm performs classification of strides and identification of FOG types. RESULTS: The described stride classification was merged with an algorithm for stride reconstruction resulting in a useful graphical tool that allows clinicians to inspect and analyze subject's movements. CONCLUSION: The described gait assessment system can be used for detection and categorization of gait disturbances by applying rule-based classification based on stride length, stride time, and frequency of the shank segment movements. The method provides an valuable graphical interface which is easy to interpret and provides clinicians and therapists with valuable information regarding the temporal changes in gait.

[Superficial siderosis: case report and literature review].

INTRODUCTION: Superficial siderosis (SS) is caused by chronic subarachnoid bleeding and is characterized by free iron and hemosiderin deposition along the pial and subpial structures of central nervous system. SS leads to progressive and irreversible CNS damage. The most common causes of chronic subarachnoidal bleeding are tumors, head and spinal cord trauma, arteriovenous malformations and aneurysms. SS is characterized by clinical triad: sensorineural hearing loss, cerebellar ataxia and piramydal signs. Brain MR imaging is the investigation of choice for the diagnosis of SS.Typical findings include hypointensities seen on T2-weighted MR imaging around the brain, cerebellum, brain stem, spinal cord, VIII cranial nerve and atrophy of cerebellum and medulla. CASE OUTLINE: A 71-year-old female patient noticed hand tremor in the middle of the third decade of life, and later slowly progressive bilateral hearing loss. At the age of 64 she developed unsteady gate, hand clumsiness and dysarthria, to became incapable of independent walking and standing five years later. Clinical course and brain MRI findings were typical for SS, but additional investigation did not reveal the couse of subarahnoidal bleeding. CONCLUSION: SS represents a rare and under-recognized condition that must be considered in all patients with cerebellar syndrome of unknown cause. Early diagnosis of SS in some cases with identified cause of chronic bleeding allowes therapeutic interventions that may prevent further progression of the disease.

Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia.

Primary dystonia (PrD) is characterized by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. Besides DYT1/TOR1A gene, DYT6/THAP1 gene is the second gene known to cause primary pure dystonia. We screened 281 Serbian primary dystonia patients and 106 neurologically healthy control individuals for the GAG deletion in TOR1A gene and for mutations in THAP1 gene by direct sequencing. Nine subjects were found to have the GAG deletion in TOR1A gene. Four coding mutations, including two novel mutations, were identified in the THAP1 gene in five unrelated patients. Two mutations were missense, one was nonsense, and one was 24 bp duplication. None of the coding mutations were seen in 106 control individuals. In addition, one novel nucleotide change in the 5'UTR region of THAP1 gene was detected in two unrelated patients. The mutation frequency of THAP1 gene in Serbian patients with primary dystonia was 1.8 %, similar to the mutation frequency in other populations. Most of the patients reported here with THAP1 mutations had the clinical features of predominantly laryngeal or oromandibular dystonia. Our data expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical regions that are usually spared in DYT1-PrD.