{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:17:02Z","timestamp":1788315422633,"version":"build-2803163510"},"reference-count":8,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Pathogenic variants in\n AMMECR1<\/jats:italic>\n have been associated with a rare multisystem disorder characterized by midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MFHIEN). To date, most reported cases involve copy number variants or presumed loss\u2010of\u2010function alterations, with only a single prior report describing a missense variant supported by functional studies. Here, we report a patient with a heterozygous\n de novo AMMECR1<\/jats:italic>\n missense variant, NM_015365.3:c.649G>A p.(Val217Met) presenting with clinical features consistent with MFHIEN, including midface hypoplasia, partial hearing impairment, nephrocalcinosis, and elliptocytosis identified on peripheral blood smear. Comparative review of the literature highlights that while previously reported missense variants in\n AMMECR1<\/jats:italic>\n demonstrated altered intranuclear protein distribution and reduced expression in functional assays, clinical evidence supporting pathogenicity of non\u2010truncating variants remains limited. The phenotypic overlap between our patient and prior report strengthens the association between missense variations and the MFHIEN phenotype. Our findings support the pathogenic relevance of missense variation in\n AMMECR1<\/jats:italic>\n and emphasize the importance of integrating detailed phenotyping, including hematologic evaluation, with genomic data in the diagnosis of rare multisystem disorders. Additional cases and functional studies are needed to clarify genotype\u2013phenotype correlations and underlying disease mechanisms.\n <\/jats:p>","DOI":"10.1111\/cge.70209","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:35:43Z","timestamp":1782952543000},"page":"496-501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Second Report of a Missense Variant in\n \n AMMECR1<\/i>\n <\/scp>\n Causing Midface Hypoplasia, Hearing Impairment, Elliptocytosis, and Nephrocalcinosis: Case Report and Literature Review"],"prefix":"10.1111","volume":"110","author":[{"given":"Jia W.","family":"Tan","sequence":"first","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8302-7705","authenticated-orcid":false,"given":"Matheus Vernet Machado Bressan","family":"Wilke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University in St. Louis St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-2937","authenticated-orcid":false,"given":"Deepak","family":"Panwar","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva S.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3308-774X","authenticated-orcid":false,"given":"Marta","family":"Figueiral","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Mayo Clinic Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan","family":"Dikilitas","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Science Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Sas","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Hypertension Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan C.","family":"Lanpher","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Pinto e Vairo","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA"},{"name":"Department of Medicine, Division of Gastroenterology and Hepatology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Klee","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23373"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102016\u2010104100"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.01.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62669"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.galenos.2020.2020.0100"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6108"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61057"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:53:44Z","timestamp":1788314024000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":8,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cge.70209"],"URL":"https:\/\/doi.org\/10.1111\/cge.70209","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"2026-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}