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Myocilin Allele-Specific Glaucoma Phenotype Database


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Hewitt, AW, Mackey, DA and Craig, JE 2007 , 'Myocilin Allele-Specific Glaucoma Phenotype Database' , Human Mutation, vol. 29, no. 2 , pp. 207-211 , doi: 10.1002/humu.20634.

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Worldwide, glaucoma is the leading irreversible cause for
blindness and by the year 2020 it is estimated that approximately
80 million people will be affected [Quigley and Broman, 2006].
Primary open angle glaucoma (POAG; MIM] 137760) is a
neurodegenerative disorder characterized by progressive excavation
(cupping) of the optic disc with corresponding loss of
peripheral vision, and is frequently associated with elevated
intraocular pressure (IOP) [Hewitt et al., 2006b]. Although
the prevalence of POAG increases with age, a subset of patients
are diagnosed with a juvenile onset form (JOAG).
In 1997, Stone and colleagues [Kubota et al., 1997; Polansky
et al., 1997; Stone et al., 1997] identified mutations in the myocilin
(MYOC) gene (MIM] 601652; formerly: trabecular meshworkinduced
glucocorticoid response gene [TIGR]) in families affected by
autosomal dominant JOAG and POAG. MYOC maps to the
GLC1A locus at 1q24–q25 [Fingert et al., 2002]. The MYOC gene
has three exons, encoding a 504–amino acid polypeptide, which
has an N-terminal leucine zipper domain and a C-terminal
olfactomedin-like domain. The majority of the identified diseasecausing
variants are clustered in the evolutionary conserved
olfactomedin-domain of exon 3 [Fingert et al., 2002]. MYOC
mutations account for most cases of autosomal dominant JOAG and
approximately one in 30 unselected cases of POAG [Fingert et al.,
1999]. MYOC-related glaucoma is predominantly associated with an
elevated IOP and strong genotype–phenotype correlations exist within
the spectrum of MYOC mutations [Alward et al., 1998]. Interestingly,
many MYOC mutations appear to have arisen from a common founder
[Baird et al., 2003; Faucher et al., 2002; Hewitt et al., 2007b].
MYOC is expressed ubiquitously in the eye and despite some
descriptions of nonsense MYOC mutations, haploinsufficiency of
the MYOC protein has been excluded as the primary disease
mechanism [Fingert et al., 2002]. Interestingly, POAG is not
induced through genetically increasing or decreasing wild-type
MYOC expression [Gould et al., 2004], and people homozygous

Item Type: Article
Authors/Creators:Hewitt, AW and Mackey, DA and Craig, JE
Keywords: juvenile open angle glaucoma; locus-specific; trabecular meshwork-induced glucocorticoid response gene; TIGR; MYOC
Journal or Publication Title: Human Mutation
Publisher: Wiley-Liss
ISSN: 1059-7794
DOI / ID Number: 10.1002/humu.20634
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