Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene
In this paper, we report a clinically proven case of Parkinson’s disease (PD) with early onset in a patient who is a heterozygous mutation carrier of <i>ATP7B</i> (the Wilson’s disease gene). The patient was observed from 2011 to 2018 in the Center for Neurodegenerati...
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MDPI AG
2019-08-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/9/3/41 |
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| author | Ekaterina Y. Ilyechova Irina V. Miliukhina Marina N. Karpenko Iurii A. Orlov Ludmila V. Puchkova Sergey A. Samsonov |
| author_facet | Ekaterina Y. Ilyechova Irina V. Miliukhina Marina N. Karpenko Iurii A. Orlov Ludmila V. Puchkova Sergey A. Samsonov |
| author_sort | Ekaterina Y. Ilyechova |
| collection | DOAJ |
| description | In this paper, we report a clinically proven case of Parkinson’s disease (PD) with early onset in a patient who is a heterozygous mutation carrier of <i>ATP7B</i> (the Wilson’s disease gene). The patient was observed from 2011 to 2018 in the Center for Neurodegenerative Diseases, Institute of Experimental Medicine (St. Petersburg, Russia). During this period, the patient displayed aggravation of PD clinical symptoms that were accompanied by a decrease in the ceruloplasmin concentration (from 0.33 to 0.27 g/L) and an increase in serum nonceruloplasmin copper, which are typical of the late stages of Wilson’s disease. It was found that one of the alleles of exon 14 in the <i>ATP7B</i> gene, which partially codes of the nucleotide-binding domain (N-domain), carries a mutation not previously reported corresponding to Cys1079Gly substitution. Alignment of the ATP7B N-domain amino acid sequences of representative vertebrate species has shown that the Cys at 1079 position is conserved throughout the evolution. Molecular dynamic analysis of a polypeptide with Cys1079Gly substitution showed that the mutation causes profound conformational changes in the N-domain, which could potentially lead to impairment of its functions. The role of <i>ATP7B</i> gene mutations in PD development is discussed. |
| first_indexed | 2024-03-12T18:34:47Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-12T18:34:47Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-43fa144eeb9a4615a7debb06ca6d6a132023-08-02T08:04:21ZengMDPI AGJournal of Personalized Medicine2075-44262019-08-01934110.3390/jpm9030041jpm9030041Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> GeneEkaterina Y. Ilyechova0Irina V. Miliukhina1Marina N. Karpenko2Iurii A. Orlov3Ludmila V. Puchkova4Sergey A. Samsonov5International Research Laboratory of Trace Elements Metabolism, ITMO University, Kronverksky av., 49, St. Petersburg 197101, RussiaCentre for Neurodegenerative diseases, Institute of Experimental Medicine, Maluy av., Petrogradskiy district, 13, St. Petersburg 197198, RussiaDepartment of Physiology, Institute of Experimental Medicine, Pavlov str., 12, St. Petersburg 197376, RussiaInternational Research Laboratory of Trace Elements Metabolism, ITMO University, Kronverksky av., 49, St. Petersburg 197101, RussiaInternational Research Laboratory of Trace Elements Metabolism, ITMO University, Kronverksky av., 49, St. Petersburg 197101, RussiaInternational Research Laboratory of Trace Elements Metabolism, ITMO University, Kronverksky av., 49, St. Petersburg 197101, RussiaIn this paper, we report a clinically proven case of Parkinson’s disease (PD) with early onset in a patient who is a heterozygous mutation carrier of <i>ATP7B</i> (the Wilson’s disease gene). The patient was observed from 2011 to 2018 in the Center for Neurodegenerative Diseases, Institute of Experimental Medicine (St. Petersburg, Russia). During this period, the patient displayed aggravation of PD clinical symptoms that were accompanied by a decrease in the ceruloplasmin concentration (from 0.33 to 0.27 g/L) and an increase in serum nonceruloplasmin copper, which are typical of the late stages of Wilson’s disease. It was found that one of the alleles of exon 14 in the <i>ATP7B</i> gene, which partially codes of the nucleotide-binding domain (N-domain), carries a mutation not previously reported corresponding to Cys1079Gly substitution. Alignment of the ATP7B N-domain amino acid sequences of representative vertebrate species has shown that the Cys at 1079 position is conserved throughout the evolution. Molecular dynamic analysis of a polypeptide with Cys1079Gly substitution showed that the mutation causes profound conformational changes in the N-domain, which could potentially lead to impairment of its functions. The role of <i>ATP7B</i> gene mutations in PD development is discussed.https://www.mdpi.com/2075-4426/9/3/41Parkinson’s diseaseWilson’s diseasecopper-status indexN-domain of ATP7Bmolecular modeling |
| spellingShingle | Ekaterina Y. Ilyechova Irina V. Miliukhina Marina N. Karpenko Iurii A. Orlov Ludmila V. Puchkova Sergey A. Samsonov Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene Journal of Personalized Medicine Parkinson’s disease Wilson’s disease copper-status index N-domain of ATP7B molecular modeling |
| title | Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene |
| title_full | Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene |
| title_fullStr | Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene |
| title_full_unstemmed | Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene |
| title_short | Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the <i>ATP7B</i> Gene |
| title_sort | case of early onset parkinson s disease in a heterozygous mutation carrier of the i atp7b i gene |
| topic | Parkinson’s disease Wilson’s disease copper-status index N-domain of ATP7B molecular modeling |
| url | https://www.mdpi.com/2075-4426/9/3/41 |
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