Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness.

PubMed ID: 27889061

Author(s): George A, Zand DJ, Hufnagel RB, Sharma R, Sergeev YV, Legare JM, Rice GM, Scott Schwoerer JA, Rius M, Tetri L, Gamm DM, Bharti K, Brooks BP. Biallelic mutations in MITF cause coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. Am J Hum Genet. 2016 Dec 1;99(6):1388-1394. doi: 10.1016/j.ajhg.2016.11.004. Epub 2016 Nov 23. PMID 27889061

Journal: American Journal Of Human Genetics, Volume 99, Issue 6, Dec 2016

Human MITF is, by convention, called the “microphthalmia-associated transcription factor” because of previously published seminal mouse genetic studies; however, mutations in MITF have never been associated with microphthalmia in humans. Here, we describe a syndrome that we term COMMAD, characterized by coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. COMMAD is associated with biallelic MITF mutant alleles and hence suggests a role for MITF in regulating processes such as optic-fissure closure and bone development or homeostasis, which go beyond what is usually seen in individuals carrying monoallelic MITF mutations.