{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:49:45Z","timestamp":1791420585944,"version":"4.3.3"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in\n                    <jats:italic>MITF<\/jats:italic>\n                    (Microphthalmia Transcription Factor) gene are associated with a spectrum of disorders, including Waardenburg syndrome type II and Tietz syndrome. Rare reports suggest that biallelic loss\u2010of\u2010function variants may result in a severe multisystem phenotype. We report an infant presenting with a phenotype consistent with COMMAD\u2010like syndrome (Coloboma, \u039fsteopetrosis, \u039cicrophthalmia, \u039cacrocephaly, \u0391lbinism, and Deafness) who died in the early neonatal period. In addition to the core COMMAD features, the proband exhibited ectopic ossification, cardiac fibrosis and fibroelastosis, interstitial lung disease, ectopic renal tissue, liver steatosis, and hemosiderosis. Whole\u2010exome sequencing identified two heterozygous truncating\n                    <jats:italic>MITF<\/jats:italic>\n                    variants, the previously reported c.961C&gt;T (p.Arg321Ter) and a novel c.1135A&gt;T (p.Lys379Ter) variant, both predicted to result in impaired MITF function. Parental testing was declined, precluding determination of the phase of the variants. To date, only one study has reported an association between biallelic MITF disruption and a severe clinical phenotype. Our findings provide additional evidence for this genotype\u2013phenotype relationship and further expand the clinical spectrum of COMMAD syndrome. The present case further supports a role for impaired MITF function in the pathogenesis of a severe multisystem phenotype.\n                  <\/jats:p>","DOI":"10.1111\/cge.70260","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:55:53Z","timestamp":1791417353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Truncating\n                    <i>MITF<\/i>\n                    Variants Expand the Phenotypic Spectrum of\n                    <scp>COMMAD<\/scp>\n                    Syndrome"],"prefix":"10.1111","author":[{"given":"Andreas","family":"Pampanos","sequence":"first","affiliation":[{"name":"Department of Genetics Alexandra General Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia\u2010E.","family":"Kostantinidou","sequence":"additional","affiliation":[{"name":"Paediatric\u2010Perinatal Pathology Unit, 1st Department of Pathology, Medical School National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-2922","authenticated-orcid":false,"given":"Maria","family":"Tzetis","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Medical School National and Kapodistrian University of Athens  Athens Greece"},{"name":"Medical Genetics Laboratory GeneTech Analytics Ltd.  Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3856-0090","authenticated-orcid":false,"given":"Vassilis","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Department of Genetics Alexandra General Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Falaina","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit General Hospital of Nikaia\u2010Piraeus \u201cAg. Panteleimon\u201d  Pireus Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-9331","authenticated-orcid":false,"given":"Aspasia","family":"Tsezou","sequence":"additional","affiliation":[{"name":"Medical Genetics Laboratory GeneTech Analytics Ltd.  Larissa Greece"},{"name":"Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine University of Thessaly  Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2806"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.324657.119"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.38.072902.092717"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15101258"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010021\u201000529\u20100"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12611"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(93)90429\u2010T"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201013359\u20108"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077149"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2020.110014"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23792"},{"issue":"3","key":"e_1_2_10_14_1","first-page":"259","article-title":"A Syndrome of Deaf\u2010Mutism Associated With Albinism Showing Dominant Autosomal Inheritance","volume":"15","author":"Tietz W.","year":"1963","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12030"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.11.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt285"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.29245\/2572-9411\/2017\/6.1118"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.181008"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells15080719"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:55:54Z","timestamp":1791417354000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":20,"alternative-id":["10.1111\/cge.70260"],"URL":"https:\/\/doi.org\/10.1111\/cge.70260","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"2026-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cge.70260"}}