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.
Aman George  1 ,  Dina J Zand  2 ,  Robert B Hufnagel  1 ,  Ruchi Sharma  3 ,  Yuri V Sergeev  1 ,  Janet M Legare  4 ,  Gregory M Rice  4 ,  Jessica A Scott Schwoerer  5 ,  Mariana Rius  1 ,  Laura Tetri  4 ,  David M Gamm  6 ,  Kapil Bharti  3 ,  Brian P Brooks  7
Affiliations
  • 1. Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • 2. Children's National Medical Center, Washington, DC 20010, USA.
  • 3. Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • 4. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
  • 5. McPherson Eye Research Institute and Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
  • 6. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA; McPherson Eye Research Institute and Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
  • 7. Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA; Children's National Medical Center, Washington, DC 20010, USA. Electronic address: [email protected].
PMID: 27889061 DOI: 10.1016/j.ajhg.2016.11.004
Abstract

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.