title: Submicroscopic deletions at 13q32.1 cause congenital microcoria.
abstract: Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR.
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Lucas
authors.initials: L
authors.lastname: Fares-Taie
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gerber
authors.affiliation: Department of Ophthalmology, University of Occupational & Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tawara
authors.affiliation: Department of Cornea and Refractive Surgery, Instituto de Oftalmologia "Conde de Valenciana," UNAM, Mexico City, DF 06800, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ramirez-Miranda
authors.affiliation: Veterinary School of Toulouse, University of Toulouse, 31300 Toulouse, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douet
authors.affiliation: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors.forename: Hannah
authors.initials: H
authors.lastname: Verdin
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Guilloux
authors.affiliation: Department of Genetics-Research Unit, Instituto de Oftalmologia "Conde de Valenciana" and Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, DF 06800, Mexico.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zenteno
authors.affiliation: Department of Ophthalmology, University of Occupational & Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Moisset
authors.affiliation: UMR1313 Génétique Animale et Biologie Intégrative, Institut Nationale de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Passet
authors.affiliation: Division of Genome Analysis, Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan; National Hospital Organization, Ehime Medical Center, Tohon, Ehime 791-0281, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.affiliation: Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-0034 Tokyo, Japan; Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, 113-0034 Tokyo, Japan; Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Kimura Eye Clinic, Kure 737-0046, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kimura
authors.affiliation: Genomics Platform, IMAGINE Foundation and Paris Descartes University, 75015 Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.affiliation: UMR1313 Génétique Animale et Biologie Intégrative, Institut Nationale de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
authors.forename: Marthe
authors.initials: M
authors.lastname: Vilotte
authors.affiliation: Service de Génétique Clinique, CHU Hôpital Sud, 35203 Rennes, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.affiliation: UMR1313 Génétique Animale et Biologie Intégrative, Institut Nationale de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vilotte
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.affiliation: Veterinary School of Toulouse, University of Toulouse, 31300 Toulouse, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Regnier
authors.affiliation: Service de Génétique Clinique, Hôpital Purpan, 31300 Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.affiliation: Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.affiliation: Veterinary School of Toulouse, University of Toulouse, 31300 Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raymond-Letron
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.affiliation: Service de Génétique Clinique, Hôpital Purpan, 31300 Toulouse, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.affiliation: Department of Ophthalmology, IHU Necker-Enfants Malades, University Paris-Descartes, 75015 Paris, France. Electronic address: oph.roche@free.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Roche
authors.affiliation: Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France. Electronic address: jean-michel.rozet@inserm.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D040461:Gene Components; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D011681:Pupil Disorders / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D017422:Sequence Analysis, DNA
chemical_list: C478763:GPR180 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D006836:Hydro-Lyases