Marios Panas

Episodes of generalized weakness in two sibs with the C164T mutation of the connexin 32 gene

Two sibs with Charcot–Marie–Tooth disease had repeated episodes of generalized weakness. The patients had distal weakness and atrophy as well as findings of CNS involvement on brain MRI. Both patients bear the C164T mutation of the connexin 32 gene but no mutations of the genes responsible for hyper- or hypokalemic periodic paralysis. It is possible that both patients have one disease with complex phenotype due to abnormal expression of the connexin 32 gene.

Apolipoprotein E polymorphism in the Greek population

The APOE gene is located on chromosome 19, and the three common alleles are designated ε2, ε3, and ε4. The ε4 allele is associated with increased plasma cholesterol, atherosclerosis and cardiovascular disease, Alzheimers disease, and decreased longevity. The objective of the present study was to estimate the distribution of APOE alleles in the Greek population by DNA analysis. The material consisted of 216 voluntary, healthy Greek blood donors (146 males/70 females). The APOE allele frequencies were ε2: 5.3%, ε3: 88.2%, ε4: 6.5%. The ε4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world.

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

The polyglutamine diseases, including Huntingtons disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases.

Apolipoprotein E and presenilin-1 genotypes in Huntington's disease

Abstract Huntington’s disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer’s disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20–65) we determined number of CAG repeats and the distribution of the APOE alleles (ɛ2, ɛ3, ɛ4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the ɛ4 allele (51.6 vs. 38.0 P < 0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the ɛ3/ɛ3 genotype while it was not detected in patients with ɛ3/ɛ4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington’s disease.

APOE ε4 is associated with impaired verbal learning in patients with MS

Objective: To investigate the effect of APOE ε4 on different cognitive domains in a population of Greek patients with multiple sclerosis (MS). Methods: A total of 125 patients with MS and 43 controls were included in this study and underwent neuropsychological assessment with Rao’s Brief Repeatable Battery. All patients with MS were genotyped for APOE. The effect of APOE ε4 on different cognitive domains was investigated. Results: Fifty-one percent of patients with MS were cognitively impaired. E4 carriers had a sixfold increase in the relative risk of impairment in verbal learning vs noncarriers (OR 6.28, 95% CI 1.74 to 22.69). This effect was domain-specific and was not observed in other cognitive domains assessed by the battery. Conclusion: We found an association of APOE ε4 with impaired verbal learning in patients with multiple sclerosis.

Huntington's disease in Greece: the experience of 14 years.

Panas M, Karadima G, Vassos E, Kalfakis N, Kladi A, Christodoulou K, Vassilopoulos D. Huntingtons disease in Greece: the experience of 14 years.

Hereditary neuropathy with liability to pressure palsies emerging during vincristine treatment

Vincristine treatment is often the cause of peripheral neuropathy, usually reversible after the discontinuation of treatment or dose reduction.1 There are several reports of acute neurotoxicity caused by the vincristine treatment of patients with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1A [CMT-1A]).2 Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited recurrent focal demyelinating neuropathy, characterized by painless nerve palsies at common sites of compression and entrapment of peripheral nerves. The most common cause of HNPP is a DNA deletion of a 1.5 Mb region on chromosome 17p11.2-p12, which includes the peripheral myelin protein (PMP) 22 gene (duplication of which causes CMT-1A).3 We report the case of a 37-year-old man with HNPP, revealed after vincristine treatment for non-Hodgkin lymphoma. A 37-year-old man developed a predominantly diffuse, large T-cell type non-Hodgkin lymphoma of intermediate grade, stage III. The patient received introduction chemotherapy with the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, consisting of a total dose of cyclophosphamide 1,500 mg IV, doxorubicin 100 mg IV, and vincristine 2 mg IV, …

C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population

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.

Migraine with aura : Segregation analysis and heritability estimation

A genetic study was performed in a group of 60 migraine patients and their first‐degree relatives as well as in a group of sex‐ and age‐matched controls. Segregation analysis showed that multifactorial inheritance seems to be the most probable mode of genetic transmission. Heritabilities were estimated according to the sex of probands and relatives.

Higher Levels of Extroverted Hostility Detected in Gene Carriers at Risk for Huntington’s Disease

BACKGROUND Numerous retrospective studies have reported the presence of psychiatric disorders at the prodromal or early stages of Huntingtons disease (HD). However, most of the studies comparing gene carriers with non-carriers before the clinical manifestation of the illness have failed to reveal differences in the psychiatric manifestation. The objective of the present study was to detect behavioral and psychological features that differentiate gene carriers from non-carriers. METHODS Eighty-one Greek patients at 50% risk for HD were recruited prospectively and examined by means of a semi-structured interview and four self-rated questionnaires. The study focused predominantly on hostility/irritability and obsessional behavior. RESULTS Gene carriers had significantly higher extroverted hostility than non-carriers (p = .005). The elevated level of hostility was unaffected by the proximity to the estimated age of onset. The remainder of the scales did not reveal significant differences. CONCLUSIONS Extroverted hostility, in particular criticism of others and delusional hostility, is increased in gene carriers well before the onset of clinical HD. Hostility is regarded as a personality dimension rather than as a behavioral pattern.