TY - JOUR
T1 - Null Mutations in LTBP2 Cause Primary Congenital Glaucoma
AU - Ali, Manir
AU - McKibbin, Martin
AU - Booth, Adam
AU - Parry, David A.
AU - Jain, Payal
AU - Riazuddin, S. Amer
AU - Hejtmancik, J. Fielding
AU - Khan, Shaheen N.
AU - Firasat, Sabika
AU - Shires, Mike
AU - Gilmour, David F.
AU - Towns, Katherine
AU - Murphy, Anna Louise
AU - Azmanov, Dimitar
AU - Tournev, Ivailo
AU - Cherninkova, Sylvia
AU - Jafri, Hussain
AU - Raashid, Yasmin
AU - Toomes, Carmel
AU - Craig, Jamie
AU - Mackey, David A.
AU - Kalaydjieva, Luba
AU - Riazuddin, Sheikh
AU - Inglehearn, Chris F.
N1 - Funding Information:
We thank the families for their support and cooperation in this work. This research was supported by the MRC (grant G0501050), the Yorkshire Eye Research (grant 009), the Higher Education Commission (Islamabad, Pakistan), the Ministry of Science and Technology (Islamabad, Pakistan), the Australia India Strategic Research Fund (grant BF020055), and the COMSTECH.EMRO project of the World Health Organization (No. RAB and GH 06-07_24). C.T. is a Royal Society University Research Fellow.
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone.
AB - Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone.
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U2 - 10.1016/j.ajhg.2009.03.017
DO - 10.1016/j.ajhg.2009.03.017
M3 - Article
C2 - 19361779
AN - SCOPUS:65149084930
SN - 0002-9297
VL - 84
SP - 664
EP - 671
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -