Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria.

Lucas Fares-Taie (1) , Sylvie Gerber (1) , Akihiko Tawara (2) , Arturo Ramirez-Miranda (3) , Jean-Yves Douet (4) , Hannah Verdin (5) , Antoine Guilloux (1) , Juan C Zenteno (3) , Hiroyuki Kondo (2) , Hugo Moisset (1) , Bruno Passet (6) , Ken Yamamoto (7) , Masaru Iwai (8, 9, 10) , Toshihiro Tanaka (11, 12) , Yusuke Nakamura (13) , Wataru Kimura (14) , Christine Bole-Feysot (15) , Marthe Vilotte (6) , Sylvie Odent (16, 17) , Jean-Luc Vilotte (6) , Arnold Munnich (1) , Alain Regnier (4) , Nicolas Chassaing (18) , Elfride de Baere (5) , Isabelle Raymond-Letron (4) , Josseline Kaplan (1) , Patrick Calvas (18) , Olivier Roche (19) , Jean-Michel Rozet (1)

1 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
2 UEOH - University of Occupational and Environmental Health [Kitakyushu]
3 Instituto de Oftalmologia Fundacion Conde de la Valenciana AC
4 ENVT - Ecole Nationale Vétérinaire de Toulouse
5 Center for Medical Genetics [Ghent]
6 GABI - Génétique Animale et Biologie Intégrative
7 Kyushu University
8 Ehime University [Matsuyama, Japon]
9 Ehime University Graduate School of Medecine
10 Ehime Medical Center
11 Tokyo Medical and Dental University
12 RIKEN IMS - Laboratory for Cardiovascular Genomics and Informatics [Yokohama]
13 University of Chicago
14 Kimura Eye Clinic
15 Plateforme de génomique [SFR Necker]
16 CHU Pontchaillou [Rennes]
17 IGDR - Institut de Génétique et Développement de Rennes
18 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
19 CHU Necker - Enfants Malades [AP-HP]

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.

Domains: Life Sciences [q-bio]

Lucas Fares-Taie, Sylvie Gerber, Akihiko Tawara, Arturo Ramirez-Miranda, Jean-Yves Douet, et al.. Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria.. American Journal of Human Genetics, 2015, 96 (4), pp.631-639. ⟨10.1016/j.ajhg.2015.01.014⟩. ⟨hal-01134461⟩