Contributors: Imagine - Institut des maladies génétiques (IMAGINE - U1163); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM); University of Occupational and Environmental Health Kitakyushu (UEOH); Instituto de Oftalmologia Fundacion Conde de la Valenciana AC; Ecole Nationale Vétérinaire de Toulouse (ENVT); Institut National Polytechnique (Toulouse) (Toulouse INP); Université de Toulouse (UT)-Université de Toulouse (UT); Center for Medical Genetics Ghent; Ghent University Hospital; Génétique Animale et Biologie Intégrative (GABI); Institut National de la Recherche Agronomique (INRA)-AgroParisTech; Kyushu University; Ehime University Matsuyama, Japon; Ehime Medical Center; Tokyo Medical and Dental University; Laboratory for Cardiovascular Genomics and Informatics Yokohama (RIKEN IMS); RIKEN Center for Integrative Medical Sciences Yokohama (RIKEN IMS); RIKEN - Institute of Physical and Chemical Research Japon (RIKEN)-RIKEN - Institute of Physical and Chemical Research Japon (RIKEN); University of Chicago; Kimura Eye Clinic; Plateforme de génomique SFR Necker; Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Institut de Génétique et Développement de Rennes (IGDR); Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre Hospitalier Universitaire de Toulouse (CHU Toulouse); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); This work was supported by grants from the Fédération des Aveugles de France (FAF) to LFT, Retina France to JMR and Geniris to JMR and PC, the Ministry of Education, Culture, Sport, Science and Technology of Japan Grant-in-aid N°20592067 to AT and the Conde de Valenciana Foundation patronage to ARM and JCZ.; ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010)
نبذة مختصرة : International audience ; 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.
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