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Background: The p.A53T variant in the SNCA gene was considered, until recently, to be the only SNCA variant causing familial Parkinson's disease (PD) in the Greek population. We identified a novel heterozygous p.A30G (c.89 C>G) SNCA pathogenic variant in five affected individuals of three Greek families, leading to autosomal dominant PD. This study aims to further explore the presence and phenotypic expression of this variant in the Greek PD population., Methods: Restriction fragment length polymorphism (RFLPs) was used for genotyping of 664 Greek PD cases. Detailed clinical information was obtained for the carriers and p.A30G-positive samples underwent haplotype analysis., Results: We identified 10 additional p.A30G-positive PD patients (1.5%), of whom 4 were sporadic cases (0.9%). They manifested typical Parkinsonian motor dysfunction, with a mean age of onset of 51.7 years (range: 33-62) and a broad spectrum of non-motor symptoms. The absence of affected first degree relatives in four out of ten index cases, and the presence of a phenocopy in an additional family, suggest that the p.A30G variant manifests reduced penetrance. The common haplotype among the p.A30G carriers confirmed a founder effect. Furthermore, two asymptomatic carriers were identified, with possible premotor manifestations., Conclusions: These findings underscore that the p.A30G SNCA pathogenic variant represents an important, albeit rare, cause of genetic PD in the Greek population. This is the first time in which a genetic synucleinopathy, with a variant in the SNCA gene, is clearly linked to an appreciable frequency of sporadic PD in a particular population., (© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Late-onset cerebellar ataxia (LOCA) is a slowly progressive cerebellar disorder with symptom onset ≥30years of age. Intronic tandem repeat expansions (TREs) in RFC1 and FGF14 have recently emerged as common causes of LOCA. The relative contribution of classic vs. newly discovered TREs has not been systematically investigated in LOCA cohorts., Methods: Over 28 years, 206 consecutive Greek LOCA index patients were referred for genetic testing and, based on clinical data and inheritance pattern, screened for FRDA, SCA1,2,3,6,7, FXTAS, CANVAS and SCA27B., Results: A genetic diagnosis was reached in 62 of 206 cases (30.1 %). Mean age was 60.1 ± 11.2 (35-87) years and mean age at onset (AAO) 52.5 ± 11.4 (30-80) years. SCA27B accounted for 9.7 % of LOCA cases, CANVAS for 7.8 % and FRDA for 4.4 %. The overall frequency of SCA1, SCA2 and SCA7 was 6.8 %. No cases of SCA3 and SCA6 were identified. FXTAS contributed 1.5 % of cases. In sporadic cases, the diagnostic yield was 22.8 % (34 of 149; SCA27B: 8.7 %, CANVAS: 8.1 %, FRDA: 2.7 %, SCA2: 1.3 %, FXTAS: 1.3 % and SCA7: 0.7 %). In familial cases, the diagnostic yield was 49.1 % (28 of 57). Two cases with CANVAS had pseudodominant inheritance. Patients with SCA27B, CANVAS and FXTAS had mean AAO > 50 years, whereas patients with FRDA, SCA1, SCA2 and SCA7 had mean AAO < 50 years., Conclusion: Recently-discovered TREs causing SCA27B and CANVAS represent the commonest known genetic causes of LOCA. Prioritizing testing for FGF14 and RFC1 expansions in the diagnostic algorithm of LOCA is recommended., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A pathogenic GAA repeat expansion in the first intron of the fibroblast growth factor 14 gene (FGF14) has been recently identified as the cause of spinocerebellar ataxia 27B (SCA27B). We herein screened 160 Greek index cases with late-onset cerebellar ataxia (LOCA) for FGF14 repeat expansions using a combination of long-range PCR and bidirectional repeat-primed PCRs. We identified 19 index cases (12%) carrying a pathogenic FGF14 GAA expansion, a diagnostic yield higher than that of previously screened repeat-expansion ataxias in Greek LOCA patients. The age at onset of SCA27B patients was 60.5 ± 12.3 years (range, 34-80). Episodic onset (37%), downbeat nystagmus (32%) and vertigo (26%) were significantly more frequent in FGF14 expansion-positive cases compared to expansion-negative cases. Beyond typical cerebellar signs, SCA27B patients often displayed hyperreflexia (47%) and reduced vibration sense in the lower extremities (42%). The frequency and phenotypic profile of SCA27B in Greek patients was similar to most other previously studied populations. We conclude that FGF14 GAA repeat expansions are the commonest known genetic cause of LOCA in the Greek population and recommend prioritizing testing for FGF14 expansions in the diagnostic algorithm of patients with LOCA., (© 2024 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Introduction: Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied., Methods: PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). PBMCs were derived from PRKN-mutated PD patients (PRKN-PD) (n = 12), sporadic PD (sPD) (n = 21) and healthy controls (n = 21). Six of the PRKN-PD patients were heterozygous, four were compound heterozygous, and two were homozygous for PRKN variants., Results: A statistically significant decrease in PRKN expression levels was present, compared to healthy controls and sPD, in heterozygous (P = 0.019 and 0.031 respectively) and biallelic (P < 0.001 for both) PRKN-PD. PRKN expression levels in biallelic PD patients were uniformly very low and were reduced, albeit not significantly, compared to heterozygotes. Based on receiver operating characteristic analysis, low PRKN expression levels were a sensitive and extremely specific indicator for the presence of PRKN pathogenic variants., Conclusions: Assessment of PRKN mRNA levels in PBMCs may be a useful way to screen for biallelic pathogenic variants in the PRKN gene. Suspicion for certain variants in a heterozygous state may also be raised based on low PRKN mRNA levels. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Aims: Axonal forms of Charcot-Marie-Tooth disease (CMT) are classified as CMT2, distal hereditary motor neuropathy (dHMN) or hereditary sensory neuropathy (HSN) and can be caused by mutations in over 100 genes. We presently aimed to investigate for the first time the genetic landscape of axonal CMT in the Greek population., Methods: Sixty index patients with CMT2, dHMN or HSN were screened by a combination of Sanger sequencing (GJB1) and next-generation sequencing custom-made gene panel covering 24 commonly mutated genes in axonal CMT., Results: Overall, 20 variants classified as pathogenic or likely pathogenic were identified in heterozygous state in 20 index cases, representing 33.3% of the cohort. Of these, 14 were known pathogenic/likely pathogenic and six were designated as such according to ACMG classification, after in silico evaluation, testing for familial segregation and further literature review. The most frequently involved genes were GJB1 (11.7%), MPZ (5%) and MFN2 (5%), followed by DNM2 (3.3%) and LRSAM1 (3.3%). Single cases were identified with mutations in BSCL2, HSPB1 and GDAP1., Interpretation: A wide phenotypic variability in terms of severity and age of onset was noted. Given the limited number of genes tested, the diagnostic yield of the present panel compares favourably with studies in other European populations. Our study delineates the genetic and phenotypic variability of inherited axonal neuropathies in the Greek population and contributes to the pathogenicity characterization of further variants linked to axonal neuropathies., (© 2023 Peripheral Nerve Society.)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset, X-linked, neurodegenerative disorder that affects premutation carriers of the FMR1 gene. FXTAS is often misdiagnosed as spinocerebellar ataxia (SCA) or Parkinson's disease (PD). Herein, we sought to investigate the frequency, genotypic and phenotypic profile of FXTAS in two cohorts of Greek patients with late-onset movement disorders, one with cerebellar ataxia and the other with PD. In total, 90 index patients with late-onset cerebellar ataxia and 171 with PD were selected. None of the cases had male-to-male transmission. Genetic screening for the FMR1 premutation was performed using standard methodology. The FMR1 premutation was detected in two ataxia patients (2.2%) and two PD patients (1.2%). Additional clinical features in FXTAS patients from the ataxia cohort included neuropathy, mild parkinsonism, cognitive impairment and pyramidal signs. The FXTAS patients from the PD cohort had typical PD. We conclude that, in the Greek population, the FMR1 premutation is an important, albeit rare, cause of late-onset movement disorders. Routine premutation screening should be considered in SCA panel-negative late-onset ataxia cases. Directed premutation screening should be considered in all ataxia and PD cases with additional features suggestive of FXTAS. Our study highlights the importance of FMR1 genetic testing in the diagnosis of late-onset movement disorders., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Myotonic Dystrophies (DM, Dystrophia Myotonia) are autosomal dominant inherited myopathies with a high prevalence across different ethnic regions. Despite some differences, mainly due to the pattern of muscle involvement and the age of onset, both forms, DM1 and DM2, share many clinical and genetic similarities. In this study, we retrospectively analyzed the medical record files of 561 Greek patients, 434 with DM1 and 127 with DM2 diagnosed in two large academic centers between 1994-2020. The mean age at onset of symptoms was 26.2 ± 15.3 years in DM1 versus 44.4 ± 17.0 years in DM2 patients, while the delay of diagnosis was 10 and 7 years for DM1 and DM2 patients, respectively. Muscle weakness was the first symptom in both types, while myotonia was more frequent in DM1 patients. Multisystemic involvement was detected in the great majority of patients, with cataracts being one of the most common extramuscular manifestations, even in the early stages of disease expression. In conclusion, the present work, despite some limitations arising from the retrospective collection of data, is the first record of a large number of Greek patients with myotonic dystrophy and emphasizes the need for specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.

The C9ORF72 hexanucleotide repeat expansion is an established cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and has also been associated with Huntington disease (HD)-like syndromes and rarely with Parkinson's disease (PD) and Alzheimer's disease (AD). In the present study we aimed to investigate the genotypic and phenotypic profile of C9ORF72-related disorders in Greece. For this reason, 957 patients (467 with ALS, 53 with HD-like syndromes, 247 with dementia, 175 with PD and 15 with hereditary spastic paraplegia, HSP) and 321 controls were tested for the C9ORF72 repeat expansion. Forty-nine patients with ALS (10.5%), 2 with HD-like syndromes (3.8%), 13 with FTD (11.5%), 1 with AD (1.6%), and 2 with PD (1.1%) were expansion-positive. The expansion was not detected in the HSP or control groups. The results of this study provide an update on the spectrum of C9ORF72-related neurodegenerative diseases, emphasizing the importance of C9ORF72 genetic testing in Greek patients with familial and sporadic ALS and/or FTD and HD-like syndromes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Comprehensive data on variant transthyretin amyloidosis polyneuropathy (ATTRv-PN) in Greece are lacking. We presently provide an overview of ATTRv-PN in Greece, focusing on unexplored non-endemic regions of the country. In total, we identified 57 cases of ATTRv-PN diagnosed over the past 25 years, including 30 from the island of Crete, an apparent endemic region. Patients carried 10 different TTR mutations (C10R; P24S; V30M; R34G; R34T; I68L; A81T; E89Q; E89K and V94A). Carriers of the common V30M mutation constituted 54.3 % of the cohort. A known founder effect for the V30M mutation was present on the island of Crete. Non-endemic cases identified outside the island of Crete are presently reported in more detail. The age of onset ranged from 25 to 77 years, with a mean of 51.1 years. A mean diagnostic delay of 3.2 years was observed. V30M patients had earlier onset and less cardiac involvement than patients carrying other mutations. Genotype-phenotype correlations were largely consistent with published data. We conclude that, with the exception of the Cretan cluster, ATTRv-PN is not endemic in the Greek population. This makes timely diagnosis more challenging, yet absolutely essential given the availability of therapies that can alter the long-term course of the disease., Competing Interests: Conflict of Interest Statement The authors report no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) is a rare hereditary neuropathy within the Charcot-Marie-Tooth disease (CMT) spectrum, linked to mutations in the histidine triad nucleotide-binding protein 1 (HINT1) gene. HINT1-related neuropathy is particularly common in selected populations from Central and Eastern Europe but rare in Western European cohorts. It has not been investigated to date in the Greek population. We presently investigated the frequency of HINT1-neuropathy in a selected cohort of 42 Greek index patients with autosomal recessive or sporadic axonal hereditary neuropathy according to standard molecular genetics procedures. We identified 4 patients with biallelic mutations in HINT1, comprising 9.5% of all cases and 44.4% of cases also displaying neuromyotonia. The c.110G> C (p.Arg37Pro) HINT1 mutation was present in all cases (2 homozygous) and the c.250T> C (p.Cys84Arg) in 2 cases (compound heterozygous). HINT1-related neuropathy patients were characterized by early onset and neuromyotonia. Two patients had noteworthy clinical features, one case developing myoclonic epilepsy and the other displaying "adducted thumbs." We conclude that HINT1-related neuropathy is common in selected Greek patients with hereditary neuropathy within the CMT spectrum, in accordance with some, but not all, European populations., (© 2021 Peripheral Nerve Society.)

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are part of the same pathophysiological spectrum and have common genetic and cerebrospinal fluid (CSF) biomarkers. Our aim here was to identify causative gene variants in a cohort of Greek patients with FTD, ALS and FTD-ALS, to measure levels of CSF biomarkers and to investigate genotype-phenotype/CSF biomarker associations. In this cohort of 130 patients (56 FTD, 58 ALS and 16 FTD-ALS), we performed C9orf72 hexanucleotide repeat expansion analysis, whole exome sequencing and measurement of "classical" (Aβ 42 , total tau and phospho-tau) and novel (TDP-43) CSF biomarkers and plasma progranulin. Through these analyses, we identified 14 patients with C9orf72 repeat expansion and 11 patients with causative variants in other genes (three in TARDBP , three in GRN , three in VCP , one in FUS , one in SOD1 ). In ALS patients, we found that levels of phospho-tau were lower in C9orf72 repeat expansion and MAPT c.855C>T (p.Asp285Asp) carriers compared to non-carriers. Additionally, carriers of rare C9orf72 and APP variants had lower levels of total tau and Aβ 42 , respectively. Plasma progranulin levels were decreased in patients carrying GRN pathogenic variants. This study expands the genotypic and phenotypic spectrum of FTD/ALS and offers insights in possible genotypic/CSF biomarker associations.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) has been recently linked to biallelic expansions of a pentanucleotide repeat in the replication factor C subunit 1 (RFC1) gene. Herein, we sought to investigate the presence of pathological RFC1 expansions in selected Greek patients with late-onset ataxia and delineate the phenotypic spectrum of genetically confirmed CANVAS in the Greek population. We screened genetically a total of 77 selected index patients, 67 originating from a cerebellar ataxia cohort and 10 from a hereditary neuropathy cohort. We identified five index cases (6.5%) with biallelic pathological RFC1 expansions, two in the cerebellar ataxia cohort (3%) and three in the neuropathy cohort (30%). Overall, four out of five of cases with full-blown CANVAS and one case with sensory ataxic neuropathy had biallelic pathological expansions. The phenotypic spectrum of positive cases (including two affected siblings) was consistent with previous reports and implied that the sensory neuropathy may be the earliest feature in genetically confirmed CANVAS. Screening for biallelic RFC1 expansions is recommended in all cases with late-onset ataxia of unknown cause, particularly when a sensory neuropathy is present., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Introduction: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 ( PSEN1 ) related familial Alzheimer's disease (AD)., Methods: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ-secretase., Results: We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ-secretase reconstitution, it destabilizes γ-secretase-amyloid precursor protein (APP)/amyloid beta (Aβn) interactions during proteolysis, enhancing the production of longer Aβ peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid-ring arteries, and severe CAA., Discussion: We show that pure SP can precede dementia onset in PSEN1- related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP-related genes, particularly when associated with a family history of cognitive decline., Competing Interests: The authors declare no competing conflict of interest. M. Breza has received a research grant from European Academy of Neurology (EAN) and travel grants from Genesis Pharma, Teva‐ Specifar, Pfizer, Sanofi‐Genzyme. G. Koutsis has received research grants from Genesis Pharma and Teva; and consultation fees, advisory boards, and honoraria from Sanofi‐Genzyme, Genesis Pharma, Teva, Novartis, Roche, Merck, Pfizer, Specifar, and Integris Pharma. G. Karadima has received research grants from Pfizer and advisory board remuneration from Roche., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Recent evidence suggests a potential role for mixed proteinopathies in the development of clinical manifestations in patients with Huntington's disease (HD). A possible cross-talk between mutant huntingtin and α-synuclein aggregates has been postulated. Serum α-synuclein has been evaluated as a potential biomarker in patients with Parkinson's disease (PD). We presently sought to investigate serum α-synuclein levels in 38 HD patients (34 symptomatic and 4 premanifest) and compare them to 36 controls. We found that α-synuclein was elevated in HD patients vs. controls (2.49 ± 1.47 vs. 1.40 ± 1.16, p = 0.001). There was no difference in α-synuclein levels between symptomatic vs. premanifest HD, nor between HD patients receiving medication vs. treatment-naïve. Furthermore, α-synuclein levels showed no correlation with CAG2, Unified HD Rating Scale (UHDRS) motor score, age, disease duration or disease burden score. Our results provide evidence for elevated serum α-synuclein in HD and lend support to further investigating the role of α-synuclein in this disorder., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Charcot-Marie-Tooth disease type 4 C (CMT4C) is an autosomal recessive form of demyelinating peripheral neuropathy caused by mutations in SH3TC2, characterized by early onset, spine deformities, and cranial nerve involvement. We screened SH3TC2 in 50 unrelated Greek patients with suspected demyelinating Charcot-Marie-Tooth disease and pedigree compatible with recessive inheritance. All patients had been previously screened for PMP22, GJB1, and MPZ mutations. We found five previously identified pathogenic mutations in SH3TC2 distributed among 13 patients in homozygosity or compound heterozygosity (p. Arg954Stop, Arg1109Stop, Gln892Stop, Ala878Asp, and Arg648Trp). Although most cases had early onset and spine deformities were almost omnipresent, a wide phenotypic spectrum was observed. Particularly notable were two siblings with Roussy-Lévy syndrome and one patient with young-onset trigeminal neuralgia. In conclusion, mutations in SH3TC2 are responsible for 26% of Greek patients with suspected CMT4, identifying CMT4C as the most common recessive demyelinating neuropathy in the Greek population, in accordance with other Mediterranean cohorts., (© 2019 Peripheral Nerve Society.)

Objective: X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS., Methods: Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity., Results: We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS., Conclusions: We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor., Competing Interests: Competing interests: GK reports grants from Teva Pharmaceuticals and Genesis Pharma; personal fees from Novartis, Genesis Pharma, Sanofi-Genzyme and Teva Pharmaceuticals; non-financial support from Merck, Sanofi-Genzyme and Genesis Pharma; MB reports no disclosures; GV reports no disclosures; JT reports shares in a diagnostic laboratory (Tzartos Neurodiagnostics) in Athens; DK reports no disclosures; CK reports no disclosures; EK reports no disclosures; DT reports no disclosures; MA reports research grants from Biogen, Merck-Serono, Novartis, Teva, Bayer and Genzyme, as well as lecture-fees from Novartis, Teva, Biogen and Genzyme; EA reports research grants from Biogen, Merck-Serono, Novartis, and Sanofi-Aventis, as well as lecture-fees from Teva; M-EE reports consultation services and honoraria from Novartis, Biogen and Teva; CK reports research grants from Biogen, Novartis, Teva, and Merck-Serono; CP reports no disclosures; MP reports no disclosures; GK reports no disclosures., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The p. A53T mutation in the alpha-synuclein (SNCA) gene is a rare cause of autosomal dominant Parkinson's disease (PD). Although generally rare, it is particularly common in the Greek population due to a founder effect. A53T-positive PD patients often develop dementia during disease course and may very rarely present with dementia., Methods: We screened for the p. A53T SNCA mutation a total of 347 cases of Greek origin with parkinsonism and/or dementia, collected over 15 years at the Neurogenetics Unit, Eginition Hospital, University of Athens. Cases were classified into: "pure parkinsonism", "pure dementia" and "parkinsonism plus dementia"., Results: In total, 4 p. A53T SNCA mutation carriers were identified. All had autosomal dominant family history and early onset. Screening of the "pure parkinsonism" category revealed 2 cases with typical PD. The other two mutation carriers were identified in the "parkinsonism plus dementia" category. One had a diagnosis of PD dementia and the other of behavioral variant frontotemporal dementia. Screening of patients with "pure dementia" failed to identify any further A53T-positive cases., Conclusions: Our results confirm that the p. A53T SNCA mutation is relatively common in Greek patients with PD or PD plus dementia, particularly in cases with early onset and/or autosomal dominant family history., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The C9orf72 repeat expansion is a common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in European populations. A previous study has reported a high frequency of the expansion in Greek ALS. However, no data have been reported on the frequency of the expansion in Greek FTD. Currently, we investigated the frequency of the C9orfF72 expansion in a well-characterized cohort of 64 Greek FTD patients. We detected the C9orf72 repeat expansion in 9.3% of cases. Overall, 27.7% of familial and 2.2% of sporadic cases were expansion-positive. Five out of 6 cases had a diagnosis of behavioral variant FTD. All expansion-positive cases had fairly typical FTD presentations. Clinical features included motor neuron disease, Parkinsonism and hallucinations. We conclude that the overall frequency of C9orf72-positive cases in Greek FTD is high, comparable to Greek ALS, similar to some Western European, but significantly higher than some Mediterranean FTD populations.

An expanded hexanucleotide repeat in C9ORF72 has been identified as the most common genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia in many populations, including the Greek. Recently, C9ORF72 expansions were reported as the most common genetic cause of Huntington disease (HD) phenocopies in a UK population. In the present study, we screened a selected cohort of 40 Greek patients with HD phenocopies for C9ORF72 hexanucleotide repeat expansions using repeat-primed polymerase chain reaction. We identified 2 patients (5%) with pathologic expansions. The first patient had chorea, behavioral-psychiatric disturbance, cognitive impairment, and a positive family history, fulfilling the strictest criteria for HD phenocopy. The second patient was sporadic and had parkinsonism, behavioral-psychiatric disturbance, and cognitive impairment, corresponding to a broader definition of HD phenocopy. These findings identify C9ORF72 expansions as a frequent cause of HD phenocopies in the Greek population, confirming recent findings in other populations and supporting proposed diagnostic testing for C9ORF72 expansions in patients with HD-like syndromes., (Copyright © 2015 Elsevier Inc. All rights reserved.)