2. Academic Validation
  3. Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness

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

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.

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