{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:58:48Z","timestamp":1789786728974,"version":"4.0.1"},"reference-count":7,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,27]],"date-time":"2019-01-27T00:00:00Z","timestamp":1548547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"World Association of Infectious Diseases and Immunological Disorders","award":["WAidid2018_05"],"award-info":[{"award-number":["WAidid2018_05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Imerslund-Gr\u00e4sbeck syndrome (IGS) is a rare autosomal recessive disorder clinically characterized by megaloblastic anemia, benign mild proteinuria, and other nonspecific symptoms. Several pathogenetic variants in the amnionless (AMN) or cubilin (CUBN) genes have been described in IGS. We describe a case of IGS with urinary tract infection and mild but persistent proteinuria at onset in an 11-month-old female child. With the appearance of macrocytic anemia, aphthous stomatitis, and neurological signs, IGS was clinically suspected, and vitamin B12 parenteral therapy was started. Sequence analysis showed the presence of a novel intronic variant c.513+5G&gt;A of AMN, never before described in the literature, that was in compound heterozygosity with the known pathogenetic variant c.1006+34_1007-31del. Analysis extension to the parents revealed the presence of variant c.1006+34_1007-31 in the father and c.513+5G&gt;A in the mother. In the present case with IGS, the novel intronic variant of AMN was identified in \u201ctrans\u201d with a known pathogenic variant (c.1006-31 del) and the new variant was interpreted to be pathogenetic since it was not found in the public database of polymorphisms and because it was predicted to alter a donor splicing site. Our case underlines the relevance in detecting certain subtle symptoms, such as mild but persistent proteinuria associated with megaloblastic anemia, to reach a correct diagnosis of a rare but treatable disorder.<\/jats:p>","DOI":"10.3390\/ijms20030527","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T03:40:55Z","timestamp":1548733255000},"page":"527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Imerslund-Gr\u00e4sbeck Syndrome in an Infant with a Novel Intronic Variant in the AMN Gene: A Case Report"],"prefix":"10.3390","volume":"20","author":[{"given":"Alessandra","family":"Pacitto","sequence":"first","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Santa Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Stangoni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Santa Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Ceppi","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Cerri","sequence":"additional","affiliation":[{"name":"Pediatric Oncohematology Unit, Santa Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Gurdo","sequence":"additional","affiliation":[{"name":"Pediatric Oncohematology Unit, Santa Maria della Misericordia Hospital, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, Piazza Menghini 1, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-1-17","article-title":"Imerslund-Gr\u00e4sbeck syndrome (selective vitamin B12 malabsorption with proteinuria)","volume":"1","year":"2006","journal-title":"Orphanet J. 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Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/ng1098","article-title":"Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia","volume":"33","author":"Tanner","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1365-2141.2006.06133.x","article-title":"Acquired and inherited disorders of cobalamin and folate in children","volume":"134","author":"Whitehead","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00467-003-1128-y","article-title":"Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption","volume":"18","author":"Pettersson","year":"2003","journal-title":"Pediatr. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/527\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:28:54Z","timestamp":1760185734000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/3\/527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,27]]},"references-count":7,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["ijms20030527"],"URL":"https:\/\/doi.org\/10.3390\/ijms20030527","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,27]]}}}