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Am J Hum Genet. 2015 Apr 2;96(4):631-9. doi: 10.1016/j.ajhg.2015.01.014. Epub 2015 Mar 12.

Submicroscopic deletions at 13q32.1 cause congenital microcoria.

Author information

1
Laboratory of Genetics in Ophthalmology (LGO), INSERM UMR1163, IMAGINE - Institute of Genetic Diseases, Paris Descartes University, 75015 Paris, France.
2
Department of Ophthalmology, University of Occupational & Environmental Health, Kitakyushu 807-8555, Japan.
3
Department of Cornea and Refractive Surgery, Instituto de Oftalmologia "Conde de Valenciana," UNAM, Mexico City, DF 06800, Mexico.
4
Veterinary School of Toulouse, University of Toulouse, 31300 Toulouse, France.
5
Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
6
Department of Genetics-Research Unit, Instituto de Oftalmologia "Conde de Valenciana" and Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, DF 06800, Mexico.
7
UMR1313 Génétique Animale et Biologie Intégrative, Institut Nationale de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
8
Division of Genome Analysis, Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
9
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.
10
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.
11
Department of Medicine and Surgery, The University of Chicago, Chicago, IL 60637, USA.
12
Kimura Eye Clinic, Kure 737-0046, Japan.
13
Genomics Platform, IMAGINE Foundation and Paris Descartes University, 75015 Paris, France.
14
Service de Génétique Clinique, CHU Hôpital Sud, 35203 Rennes, France.
15
Service de Génétique Clinique, Hôpital Purpan, 31300 Toulouse, France.
16
Department of Ophthalmology, IHU Necker-Enfants Malades, University Paris-Descartes, 75015 Paris, France. Electronic address: oph.roche@free.fr.
17
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.

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.

PMID:
25772937
PMCID:
PMC4385178
DOI:
10.1016/j.ajhg.2015.01.014
[Indexed for MEDLINE]
Free PMC Article

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