{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:38:07Z","timestamp":1761197887354,"version":"3.37.3"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Glucocerebrosidase (<jats:italic>GBA<\/jats:italic>) heterozygous variants are the most important genetic risk factor for the development of alpha-synucleinopathies (i.e., Parkinson\u2019s disease and Dementia with Lewy Bodies). Herein, we report for the first time on a patient with a clinical diagnosis of Posterior Cortical Atrophy, carrier of the common <jats:italic>GBA<\/jats:italic> heterozygous variant N370S (c.1226A\u2009&gt;\u2009G).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 44-year-old woman with positive familial history for Dementia with Lewy Bodies disclosed three related signs characterizing the Balint\u2019s syndrome: ocular apraxia, optic ataxia and simultanagnosia. Over 2-year follow up, overt gaze apraxia (psychic paralysis of gaze) appeared leading to functional blindness. Given her young age at onset and positive familial history, she underwent a next-generation-sequencing (NGS) based screening of a panel of 32 genes related to neurodegenerative conditions within the ANAMNESYS (An origiNal Approach to study faMiliarity in NEurodegenerative SYndromeS) study. NGS demonstrated the N370S variant in the <jats:italic>GBA<\/jats:italic> gene (rs76763715), confirmed by Sanger sequencing. This is a relatively common variant, with predicted mild impact, already reported to occur in 2.4% of PD Italian patients; however, neither this nor other <jats:italic>GBA<\/jats:italic> variants have ever been reported to date in patients with Posterior Cortical Atrophy. Glucocerebrosidase activity was investigated and found to be significantly reduced (4.72\u2009nmol\/h\/mg) compared to healthy controls as well as patients affected by neurodegenerative diseases, further supporting pathogenicity of the <jats:italic>GBA<\/jats:italic> variant.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We report on a patient with a clinical diagnosis of Posterior Cortical Atrophy, carrier of the <jats:italic>GBA<\/jats:italic> heterozygous variant N370S (c.1226A\u2009&gt;\u2009G; p.Asn409Ser) determining reduced GCase activity. This report also confirms the role of NGS-based targeted gene analysis in detecting peculiar clinical phenotypes associated with known pathogenic mutations and reinforces the knowledge that carriers of genetic variants often present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria in defining boundaries between distinct conditions and the difficulties of clinicians in reaching the best clinical diagnosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-020-02023-5","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T06:15:48Z","timestamp":1610432148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Posterior Cortical Atrophy phenotype in a GBA N370S mutation carrier: a case report"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-137X","authenticated-orcid":false,"given":"Marina","family":"Picillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Scannapieco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Iavarone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monia","family":"Ginevrino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Barone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"issue":"5","key":"2023_CR1","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/ana.24777","volume":"80","author":"R Cilia","year":"2016","unstructured":"Cilia R, Tunesi S, Marotta G, et al. Survival and dementia in GBA-associated Parkinson's disease: the mutation matters. Ann Neurol. 2016;80(5):662\u201373.","journal-title":"Ann Neurol"},{"issue":"3","key":"2023_CR2","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/mdc3.12406","volume":"4","author":"M Picillo","year":"2016","unstructured":"Picillo M, Petrucci S, Valente EM, et al. Progressive Supranuclear palsy-like phenotype in a GBA E326K mutation carrier. Mov Disord Clin Pract. 2016;4(3):444\u20136.","journal-title":"Mov Disord Clin Pract"},{"key":"2023_CR3","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/ene.12894","volume":"23","author":"A Pilotto","year":"2016","unstructured":"Pilotto A, Schulte C, Hauser AK. GBA-associated parkinsonism and dementia: beyond \u03b1-synucleinopathies? Eur J Neurol. 2016;23:520\u20136.","journal-title":"Eur J Neurol"},{"issue":"8","key":"2023_CR4","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.jalz.2017.01.014","volume":"13","author":"SJ Crutch","year":"2017","unstructured":"Crutch SJ, Schott JM, Rabinovici GD, et al. Alzheimer's Association ISTAART atypical Alzheimer's disease and associated syndromes professional interest area. Consensus classification of posterior cortical atrophy. Alzheimers Dement. 2017;13(8):870\u201384.","journal-title":"Alzheimers Dement"},{"issue":"1","key":"2023_CR5","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","volume":"89","author":"I McKeith","year":"2017","unstructured":"McKeith I, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with LEwy bodies: fourth consensus of the DLB consortium. Neurology. 2017;89(1):88\u2013100.","journal-title":"Neurology"},{"key":"2023_CR6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3389\/fncel.2018.00125","volume":"12","author":"S Cerri","year":"2018","unstructured":"Cerri S, Ghezzi C, Sampieri M, et al. The exosomal\/total alpha-synuclein ratio in plasma is associated with glucocerebrosidase activity and correlates with measures of disease severity in PD patients. Front Cell Neurosci. 2018;12:125.","journal-title":"Front Cell Neurosci"},{"key":"2023_CR7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.parkreldis.2015.12.002","volume":"23","author":"HJ Kim","year":"2016","unstructured":"Kim HJ, Jeon B, Song J, Lee WW, Park H, Shin CW. Leucocyte glucocerebrosidase and Beta-hexosaminidase activity in sporadic and genetic Parkinson disease. Parkinsonism Relat Disord. 2016;23:99\u2013101.","journal-title":"Parkinsonism Relat Disord"},{"issue":"10","key":"2023_CR8","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1136\/jnnp-2019-320394","volume":"90","author":"M Avenali","year":"2019","unstructured":"Avenali M, Toffoli M, Mullin S, et al. Evolution of prodromal parkinsonian features in a cohort of GBA mutation-positive individuals: a 6-year longitudinal study. J Neurol Neurosurg Psychiatry. 2019;90(10):1091\u20137.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2023_CR9","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.parkreldis.2014.09.003","volume":"20","author":"R Asselta","year":"2014","unstructured":"Asselta R, Rimoldi V, Siri C, et al. Glucocerebrosidase mutations in primary parkinsonism. Parkinsonism Relat Disord. 2014;20:1215\u201320.","journal-title":"Parkinsonism Relat Disord"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-02023-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12883-020-02023-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-020-02023-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:24:07Z","timestamp":1610483047000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-020-02023-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,12]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2023"],"URL":"https:\/\/doi.org\/10.1186\/s12883-020-02023-5","relation":{},"ISSN":["1471-2377"],"issn-type":[{"type":"electronic","value":"1471-2377"}],"subject":[],"published":{"date-parts":[[2021,1,12]]},"assertion":[{"value":"10 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The present study was approved by the local ethics committee (Campania sud \u2013 n.91 21\/07\/2016) and the patient was included upon signature of informed consent form.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patient provided written consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests. Marina Picillo is supported by the Michael J Fox Foundation for Parkinson\u2019s research; Paolo Barone received consultancies as a member of the advisory board for Zambon, Lundbeck, UCB, Chiesi, Abbvie and Acorda; the other authors report no financial diclosures for the previous 12\u2009months.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}