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, 6)
,
Hiroyuki Kondo
(2)
,
Hugo Moisset
(1)
,
Bruno Passet
(7)
,
Ken Yamamoto
(8)
,
Masaru Iwai
(9, 10)
,
Toshihiro Tanaka
(11, 12, 13)
,
Yusuke Nakamura
(14)
,
Wataru Kimura
(15)
,
Christine Bole-Feysot
(1)
,
Marthe Vilotte
(7)
,
Sylvie Odent
(16)
,
Jean-Luc Vilotte
(7)
,
Arnold Munnich
(1)
,
Alain Regnier
(4)
,
Nicolas Chassaing
(17, 18)
,
Elfride De baere
(5)
,
Isabelle Raymond-Letron
(4)
,
Josseline Kaplan
(1)
,
Patrick Calvas
(17, 18)
,
Olivier Roche
(19, 20)
,
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 UNAM - Universidad Nacional Autónoma de México = National Autonomous University of Mexico
7 GABI - Génétique Animale et Biologie Intégrative
8 Kyushu University
9 Ehime University [Matsuyama, Japon]
10 Ehime Medical Center
11 Kagoshima University Graduate School of Medical and Dental Sciences
12 TMDU - Tokyo Medical and Dental University [Japan]
13 RIKEN IMS - RIKEN Center for Integrative Medical Sciences [Yokohama]
14 The University of Chicago Medicine [Chicago]
15 Kimura Eye Clinic
16 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
17 UDEAR - Unité différenciation épidermique et auto-immunité rhumatoïde
18 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
19 Hôpital Necker - Enfants Malades [AP-HP]
20 UPD5 - Université Paris Descartes - Paris 5
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 UNAM - Universidad Nacional Autónoma de México = National Autonomous University of Mexico
7 GABI - Génétique Animale et Biologie Intégrative
8 Kyushu University
9 Ehime University [Matsuyama, Japon]
10 Ehime Medical Center
11 Kagoshima University Graduate School of Medical and Dental Sciences
12 TMDU - Tokyo Medical and Dental University [Japan]
13 RIKEN IMS - RIKEN Center for Integrative Medical Sciences [Yokohama]
14 The University of Chicago Medicine [Chicago]
15 Kimura Eye Clinic
16 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
17 UDEAR - Unité différenciation épidermique et auto-immunité rhumatoïde
18 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
19 Hôpital Necker - Enfants Malades [AP-HP]
20 UPD5 - Université Paris Descartes - Paris 5
Bruno Passet
- Fonction : Auteur
- PersonId : 749139
- IdHAL : bruno-passet
Jean-Luc Vilotte
- Fonction : Auteur
- PersonId : 184316
- IdHAL : jean-luc-vilotte
- ORCID : 0000-0003-4623-0584
- IdRef : 076358070
Nicolas Chassaing
- Fonction : Auteur
- PersonId : 902643
Patrick Calvas
- Fonction : Auteur
- PersonId : 853869
Résumé
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.