title: Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness.
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.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Aman
authors.initials: A
authors.lastname: George
authors.affiliation: Children's National Medical Center, Washington, DC 20010, USA.
authors.forename: Dina J
authors.initials: DJ
authors.lastname: Zand
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Sergeev
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Legare
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Rice
authors.affiliation: McPherson Eye Research Institute and Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Scott Schwoerer
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Rius
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Tetri
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: Gamm
authors.affiliation: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Kapil
authors.initials: K
authors.lastname: Bharti
authors.affiliation: 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: brian.brooks1@nih.gov.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
mesh_terms: D000417:Albinism / Q000235:genetics*; D000483:Alleles; D000818:Animals; D002675:Child, Preschool; D003103:Coloboma / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics*; D010022:Osteopetrosis / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D029961:Zebrafish Proteins; C497237:mitfa protein, zebrafish