{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T04:48:14Z","timestamp":1766983694072,"version":"3.43.0"},"reference-count":20,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Nivelon\u2010Nivelon\u2010Mabille syndrome (NNMS, #600092) is an extremely rare genetic disorder characterized by microcephaly, central nervous system abnormalities, skeletal anomalies, and 46,XY disorders of sex development. It is caused by biallelic variants in the <jats:italic>HHAT<\/jats:italic> gene, which encodes the Hedgehog acyltransferase (HHAT) protein. To date, only eight patients with NNMS have been reported in the literature. In this study, four new patients from two unrelated families were presented, exhibiting distinct phenotypic features including 46,XY gonadal dysgenesis, microcephaly, microphthalmia, ocular coloboma, skeletal dysplasia, and cerebellar vermis hypoplasia. Ptosis and marked visual impairment were present only in the current study. NNMS was considered with the present clinical and radiological findings for four patients, and whole exome analysis revealed three novel variants of the <jats:italic>HHAT<\/jats:italic> gene. In silico analyses were performed to provide insights into the structural and functional effects of these genetic variants on the HHAT protein. Accurate diagnosis is crucial for increasing clinical awareness and offering genetic counseling to affected families.<\/jats:p>","DOI":"10.1002\/ajmg.a.64107","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T08:14:59Z","timestamp":1746519299000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Four New Patients of <scp><i>HHAT<\/i><\/scp>\u2010Related Multiple Congenital Anomalies Syndrome (<scp>Nivelon\u2010Nivelon\u2010Mabille Syndrome<\/scp>) and a Comprehensive Literature Review"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3814-564X","authenticated-orcid":false,"given":"Ay\u015fe Burcu Do\u011fan","family":"Ar\u0131","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics University of Health Sciences, Ankara Bilkent City Children's Hospital  Ankara 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