title: Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma.
abstract: Glaucoma is a heterogeneous group of optic neuropathies that manifests by optic nerve head cupping or degeneration of the optic nerve, resulting in a specific pattern of visual field loss. Glaucoma leads to blindness if left untreated, and is considered the second leading cause of blindness worldwide. The subgroup primary congenital glaucoma (PCG) is characterized by an anatomical defect in the trabecular meshwork, and age at onset in the neonatal or infantile period. It is the most severe form of glaucoma. CYP1B1 was the first gene genetically linked to PCG, and CYP1B1 mutations are the cause of disease in 20-100% of patients in different populations. Here, we report that LTBP2 encoding latent transforming growth factor beta binding protein 2 is a PCG causing gene, confirming results recently reported. A disease-associated locus on chromosome 14 was identified by performing whole genome autozygosity mapping in Iranian PCG families using high density single nucleotide polymorphism chips, and two disease-segregating loss of function mutations in LTBP2, p.Ser472fsX3 and p.Tyr1793fsX55, were observed in two families while sequencing candidate genes in the locus. The p.Tyr1793fsX55 mutation affects an amino acid close to the C-terminal of the encoded protein. Subsequently, LTBP2 expression was shown in human eyes, including the trabecular meshwork and ciliary processes that are thought to be relevant to the etiology of PCG.
authors: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors: Mehrnaz
authors: M
authors: Narooie-Nejad
authors: Seyed Hassan
authors: SH
authors: Paylakhi
authors: Seyedmehdi
authors: S
authors: Shojaee
authors: Zeinab
authors: Z
authors: Fazlali
authors: Mozhgan
authors: M
authors: Rezaei Kanavi
authors: Naveed
authors: N
authors: Nilforushan
authors: Shahin
authors: S
authors: Yazdani
authors: Farbod
authors: F
authors: Babrzadeh
authors: Fatemeh
authors: F
authors: Suri
authors: Mostafa
authors: M
authors: Ronaghi
authors: Elahe
authors: E
authors: Elahi
authors: Coro
authors: C
authors: Paisán-Ruiz
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005123:Eye / Q000378:metabolism; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007492:Iran; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
chemical_list: C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins