A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein

Mabuchi, Fumihiko; Yamagata, Zentaro; Kashiwagi, Kenji; Ishijima, Kiyotaka; Tang, Sa; Iijima, Hiroyuki; Tsukahara, Shigeo

doi:10.1007/s100380170114

Cited by 9 publications

(2 citation statements)

References 28 publications

(29 reference statements)

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“…Although these 3 patients were supposed to be unrelated, all of them had 1–83 bp (G→A) in the promoter and Arg76Lys simultaneously, which suggests that they are descended from a common ancestor. Results concerning about Arg158Gln have been reported in detail [28].…”

Section: Discussionmentioning

confidence: 99%

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open‐angle glaucoma

Mabuchi

Yamagata²,

Kashiwagi

et al. 2001

Clinical Genetics

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The myocilin gene was identified as a gene (MYOC) that caused primary open-angle glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the myocilin gene mutation was previously reported, no study using large numbers of patients with NTG has been reported. Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping the myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and nineteen patients with POAG and 100 control subjects without glaucoma were studied as reference subjects. Five amino acid sequence changes of the myocilin were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese, Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it was reported in Chinese. Although some Japanese patients with NTG had sequence changes of the myocilin gene, there were no apparent specific mutations in patients with NTG.

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Section: Discussionmentioning

confidence: 99%

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open‐angle glaucoma

Mabuchi

Yamagata²,

Kashiwagi

et al. 2001

Clinical Genetics

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“…locus in the year 1993 8 and subsequently linked to the MYOC gene in the year 1997, 9 there have been over 70 different point mutations in multiple ethnic groups identified worldwide. Mutations in the coding regions of MYOC are associated with 3% to 5% of POAG cases throughout the world [10][11][12][13][14][15][16][17][18][19][20][21] and account for a larger proportion of JOAG cases (from 6% to 36%). 22,23 MYOC is expressed in multiple ocular and nonocular tissues and despite intense investigation, the function of this protein is largely unknown.…”

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confidence: 99%

Glaucoma Genetics

Challa¹

2008

International Ophthalmology Clinics

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Glaucoma is one of the leading causes of blindness throughout the world 1,2 with a prevalence of over 2% in individuals over 40 years old. 3 It is a heterogeneous disorder characterized by a progressive degeneration of axons manifesting as optic nerve head cupping and field loss. Most glaucomas are asymptomatic until late in the disease course and therefore, many patients are diagnosed on routine examinations or only after advanced field loss has occurred. The molecular etiology of glaucoma is largely unknown, but there are numerous studies establishing a genetic etiology for this disorder. Mutations in specific genes are associated with the manifestations of open angle glaucoma (OAG), pseudoexfoliation glaucoma (XFG), congenital glaucoma, and the anterior segment dysgenesis syndromes. Understanding the molecular basis of glaucoma is important to several aspects of glaucoma diagnosis and management. Genetic testing could be used to identify individuals who are high risk for the development or progression of glaucoma. Identifying novel pathways could be used to design more specific and effective therapies. This article will review the genes associated with different forms of glaucoma AQ1(Table 1). OAG The most common form of glaucoma is primary open angle glaucoma (POAG), affecting over 33 million people worldwide. 1 This is a late-onset and complex disorder that is associated with elevated intraocular pressures (IOPs) leading to axonal degeneration and visual field loss. The IOP increase in this disorder seems to be owing to an "inefficiency" of the trabecular meshwork (TM) leading to decreased aqueous outflow facility. Its multifactorial etiology was first proposed in the year 1967 4 and it demonstrates a variable age of onset and severity. Most studies suggest an autosomal dominant inheritance with incomplete penetrance. 5 However, the inheritance pattern of this disorder seems to be multifactorial resulting from the interaction of one or more genes and/or environmental stimuli. To date, there have been over 20 genetic loci and 3 genes, MYOC (myocilin), OPTN (optineurin), and WDR36 that have been linked to POAG. Like POAG, juvenile open angle glaucoma (JOAG) is also characterized by the presence of elevated IOPs, optic nerve cupping, and open angles. It has a variable age of onset, but typically presents with very high IOPs from ages 3 to 25 years. Like most glaucomas, it is not a single entity, but is rather a spectrum disorder in which some individuals present with developmental immaturities of the angle with an increased number of iris processes and a thicker, more compact tissue on the inner wall of Schlemm's canal. 6 However, other JOAG individuals present with anatomic and histologic findings indistinguishable from POAG. Moreover, JOAG patients tend to be less responsive to argon laser trabeculoplasty and are often more resistive to medical therapy than POAG. Therefore, different forms of JOAG seem to be distinct from POAG and they may actually be different disorders with similar phenotypes. The first gen...

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New mutation in the MYOC gene and its association with primary open-angle glaucoma in a Chinese family

Zhou

et al. 2009

Mol Biol Rep

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Myocilin (MYOC) gene is expressed in many ocular tissues, including the trabecular meshwork, a specialized eye tissue essential in regulating intraocular pressure. Many mutations in MYOC have been detected in primary open-angle glaucoma (POAG). We investigated whether MYOC mutations contributed to the susceptibility to POAG in a Chinese family. In a four-generation family affected with POAG, ocular examinations were performed on all members of the pedigree to determine their disease status, and 200 healthy matched controls were recruited. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to determine the mutations in MYOC. Biological software was used to analyze the corresponding proteins for missense mutations. The c.1084G>- was found, for the first time, in four of eight affected patients and in one of two patients with suspected POAG. The c.1006C>T mutation was found in two of eight patients and in one of 19 subjects who were asymptomatic. The frequencies of c.1084G>- and c.1006C>T were 12.82 and 7.69%, respectively, in patients but not in the controls. These data provide additional clues to the pathogenesis of POAG because no other mutation was detected in either group. Our results suggest that the MYOC c.1084G>- may contribute to a genetic predisposition to POAG.

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A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein

Cited by 9 publications

References 28 publications

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open‐angle glaucoma

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open‐angle glaucoma

Glaucoma Genetics

New mutation in the MYOC gene and its association with primary open-angle glaucoma in a Chinese family

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