Bozi M, Papadimitriou D, Antonellou R, Moraitou M, Maniati M, Vassilatis D K, Papageorgiou S G, Leonardos A, Tagaris G, Malamis G, Theofilopoulos D, Kamakari S, Stamboulis E, Hadjigeorgiou G M, Athanassiadou A, Michelakakis H, Papadimitriou A, Gasser T, Stefanis L
Second Department of Neurology, University of Athens Medical School, Athens, Greece; Department of Neurodegenerative Diseases, 'Hygeia' Hospital, Athens, Greece.
Eur J Neurol. 2014 Jul;21(7):963-8. doi: 10.1111/ene.12315. Epub 2013 Dec 7.
Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population.
A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene.
In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations.
The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.
尽管几年前在希腊和意大利裔家族的α-突触核蛋白（SNCA）基因中首次发现了与帕金森病（PD）相关的突变，但尚未在希腊人群中对该突变及其他已知的PD突变进行更系统的研究。
对111例家族性或散发性早发型（≤50岁，EO）PD患者进行基因分析，检测A53T SNCA突变的存在情况。在这些患者的不同亚组中，进一步搜索SNCA、LRRK2、帕金、PINK1和DJ-1基因中的其他突变。此外，对一组家族性病例分析了葡萄糖脑苷脂酶（GBA）基因中的突变。
总共鉴定出5例（占全部患者的4.5%）携带A53T SNCA突变，2例携带帕金基因杂合剂量突变，1例携带帕金基因杂合点突变，7例（占家族性队列的10.3%）携带GBA基因突变。
SNCA基因中的A53T突变虽然不常见，但确实是希腊人群中PD的一个病因，尤其是常染色体显性遗传的家族性早发性帕金森病。此处检测的家族性队列中的GBA突变与之前同一中心检测的散发性病例队列中的情况一样常见。对于其余基因，未发现可明确解释该疾病的遗传缺陷。这些结果表明，希腊人群中导致PD的其他孟德尔性状仍有待发现。
