Dataset Information

Null mutations in LTBP2 cause primary congenital glaucoma.

ABSTRACT: 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.

SUBMITTER: Ali M

PROVIDER: S-EPMC2680998 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Null mutations in LTBP2 cause primary congenital glaucoma.

Ali Manir M McKibbin Martin M Booth Adam A Parry David A DA Jain Payal P Riazuddin S Amer SA Hejtmancik J Fielding JF Khan Shaheen N SN Firasat Sabika S Shires Mike M Gilmour David F DF Towns Katherine K Murphy Anna-Louise AL Azmanov Dimitar D Tournev Ivailo I Cherninkova Sylvia S Jafri Hussain H Raashid Yasmin Y Toomes Carmel C Craig Jamie J Mackey David A DA Kalaydjieva Luba L Riazuddin Sheikh S Inglehearn Chris F CF

American journal of human genetics 20090409 5

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 fo ...[more]

PMID: 19361779

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Project description:Primary congenital glaucoma (PCG) is a severe form of glaucoma that presents early in life. PCG is a clinical and genetic entity that is distinct from juvenile forms of glaucoma. Inheritance is usually autosomal recessive and therefore the disease might be more common in societies where consanguinity is high. We studied the prevalence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) and latent-transforming growth factor beta-binding protein 2 (LTBP2) mutations in a group of Saudi PCG patients and attempted to correlate the mutation status with the disease severity.Genomic DNA was collected from 54 unrelated Saudi PCG families (74 patients) who were diagnosed as having PCG by standard ophthalmological examinations and screened for mutations in CYP1B1 and LTBP2 by sequencing. We also examined the effect of mutations on the phenotype of patients with PCG (phenotype-genotype correlation).Mutations in CYP1B1 were identified in 41 (75.9%) of affected patients. No mutation in CYP1B1 was found in 13 (24.1%) affected persons. We detected a total of 13 mutations: 9 missense mutations (G61E, A119S, R390H, P437L, D441G, A443G, G466S, G466D, and R469W), 2 deletions (g.4238_4247del and g.7901_7913del), and 2 nonsense mutations (R355X and R444X). Two mutations, G466S and D441G, were novel. The G61E mutation was by far the most common mutation detected. PCG cases with CYP1B1 mutation(s) presented with a high degree of haze and greater cup/disc ratio than those with no mutation(s). Also, PCG cases with a mutation had higher post operative indices in terms of post operative haze and the need for anti-glaucoma medications. Additionally, the surgical success rate was higher 13/14 (92.9%) among cases without mutation than those with mutation 42/60 (70%). No mutation(s) were found in LTBP2 in any of the tested patients.CYP1B1 mutations are the predominant cause of PCG in the Saudi Arabian population with G61E as the dominant disease-associated allele. PCG cases with a mutation had higher last postoperative visit indices in terms of postoperative haze and the need for anti-glaucoma medications. This will be a valuable parameter in predicting disease severity earlier on and might help in predicting the surgical outcome.

Dataset Information

Null mutations in LTBP2 cause primary congenital glaucoma.

Publications

Null mutations in LTBP2 cause primary congenital glaucoma.

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