{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:36:19Z","timestamp":1760402179615,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["not available"],"award-info":[{"award-number":["not available"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007706","name":"Ministero dello Sviluppo Economico","doi-asserted-by":"publisher","award":["F\/050011\/01\/X32"],"award-info":[{"award-number":["F\/050011\/01\/X32"]}],"id":[{"id":"10.13039\/501100007706","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente"],"award-info":[{"award-number":["Ricerca corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype\u2013phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.<\/jats:p>","DOI":"10.3390\/ijms22073625","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T10:24:33Z","timestamp":1617186273000},"page":"3625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families"],"prefix":"10.3390","volume":"22","author":[{"given":"Filomena","family":"Napolitano","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9388-9336","authenticated-orcid":false,"given":"Giorgia","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-5578","authenticated-orcid":false,"given":"Chiara","family":"Terracciano","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"Neurology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Franzese","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6240-9272","authenticated-orcid":false,"given":"Nicole","family":"Palomba","sequence":"additional","affiliation":[{"name":"IRCCS INM Neuromed, Pozzilli, 86077 Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1797-9051","authenticated-orcid":false,"given":"Federica","family":"Scotto di Carlo","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Signoriello","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-7994","authenticated-orcid":false,"given":"Paolo","family":"De Blasiis","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Navarro","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, National Research Council, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-4463","authenticated-orcid":false,"given":"Alessandro","family":"Gialluisi","sequence":"additional","affiliation":[{"name":"IRCCS INM Neuromed, Pozzilli, 86077 Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-9277","authenticated-orcid":false,"given":"Mariarosa","family":"Melone","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1383-6638","authenticated-orcid":false,"given":"Simone","family":"Sampaolo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and Inter University Center for Research in Neurosciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-8441","authenticated-orcid":false,"given":"Teresa","family":"Esposito","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cAdriano Buzzati-Traverso\u201d, National Research Council, 80131 Naples, Italy"},{"name":"IRCCS INM Neuromed, Pozzilli, 86077 Isernia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Beaudet, A., Sly, W.S., and Valle, D. 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