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Year : 2003  |  Volume : 51  |  Issue : 3  |  Page : 279-281

Myocilin mutation 1109 C>T (Pro 370 Leu) is the most common gene defect causing early onset primary open angle glaucoma

Correspondence Address:
A Mukhopadhyay

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Source of Support: None, Conflict of Interest: None

PMID: 14601861

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How to cite this article:
Mukhopadhyay A, Acharya M, Ray J, Khan M, Sarkar K, Banerjee AR, Ray K. Myocilin mutation 1109 C>T (Pro 370 Leu) is the most common gene defect causing early onset primary open angle glaucoma. Indian J Ophthalmol 2003;51:279-81

How to cite this URL:
Mukhopadhyay A, Acharya M, Ray J, Khan M, Sarkar K, Banerjee AR, Ray K. Myocilin mutation 1109 C>T (Pro 370 Leu) is the most common gene defect causing early onset primary open angle glaucoma. Indian J Ophthalmol [serial online] 2003 [cited 2023 Nov 30];51:279-81. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2003/51/3/279/14664

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Dear Editor,

Glaucoma represents a heterogeneous group of neurodegenerative disorders of the eye affecting about 67 million people worldwide.[1] Primary open angle glaucoma (POAG) is the most common form of the disease, causing progressive and often silent loss of vision, and if untreated resulting in bilateral blindness. Positive family history is a significant risk factor for POAG. Unlike most other genetic diseases, identification of individuals at an early or preclinical stage of POAG provides the clinician with the opportunity to better manage the disease. This in turn could help save or extend the vision of the patient. Two different genes, Myocilin (MYOC) and Optineurin (OPTN), and four additional chromosomal loci (2cen-q13, 3q21-24, 8p23, 7q35-36) are reported to be linked to POAG.[2],[3] It is estimated that 3-4% of adult and a significant portion of juvenile open angle glaucoma is caused by MYOC and mutation in MYOC causes autosomal dominant transmission of POAG in the affected families. Fifty-seven mutations have been reported so far worldwide. Multiple mutations in the myocilin gene (136 C>T, 244 C>T, 1099 G>A, 1102 C>T, 1109 C>T, 1130 C>T, 1265 G>A, 1408 C>T), which are in CpG context, have been reported to recur in different population groups, suggesting that CpG dinucleotides serve as mutational hotspots in this gene. However, on careful examination of the literature we noticed that in this type of mutation, 1109 C>T (Pro370Leu) covers the widest range of population groups, i.e., French, Germans, Greek, Indians, Japanese and North American [Table - 1]. Furthermore, multiple occurrence of this mutation has been reported in the French population under different haplotype backgrounds.[4] Occurrence of this mutation in the CpG sequence context, its detection in diverse population groups and indentification of multiple patients in the French study in different haplotype backgrounds strongly suggest that the mutation recurs by de novo events. Unlike some of the other mutations found in sporadic POAG cases, which makes it difficult to establish a causal association of the mutation with the disease, 1109 C>T mutation has always been found to cosegregate with an early onset form of POAG in families, including those in our study.[5] The mutation could be easily detected by a PCR-RFLP assay [Figure - 1]. Thus, a 198 bp region of the genomic DNA containing the point mutation could be amplified and digested with AlwN 1 to two DNA fragments (159 bp & 39 bp) while the amplicons from the normal copy of the gene remained undigested.[5] Using this PCR-based assay we have identified this mutation in seven of 70 POAG patients selected based on the criteria described before.[5] All seven patients belong to a single large Muslim family of eastern India. By examining younger children in the family we detected three mutant children at the pre-clinical stage, which would help in early management of the disease. We predict that future mutational studies in MYOC across the globe will identify a much higher prevalence of this mutation among early onset POAG patients. We also recommend that the PCR based-assay for this particular mutation should get the top priority in any mutation screening effort in MYOC.

  References Top

Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80:389-93.  Back to cited text no. 1
Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, et al. Identification of a gene that causes primary open angle glaucoma. Science 1997;275:668-70.  Back to cited text no. 2
Rezaie T, Child A, Hitchings R, Brice G, Miller L, Coca-Prados M, et al. Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 2002;295:1077-79.  Back to cited text no. 3
Adam MF, Belmouden A, Binisti P, Brezin AP, Valtot F, Bechetoille A, et al. Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Genet 1997;6:2091-97.  Back to cited text no. 4
Mukhopadhyay A, Acharya M, Mukherjee S, Ray J, Choudhury S, Khan M, et al. Mutations in MYOC gene of Indian primary open angle glaucoma patients. Mol Vis 2002;8:442-48.  Back to cited text no. 5


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  [Table - 1]

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Molecular Vision. 2007; 13(1793): 1801
2 MYOC gene mutations in Spanish patients with autosomal dominant primary open-angle glaucoma: A founder effect in southeast Spain
Campos-Mollo, E., Sánchez-Sánchez, F., López-Garrido, M.P., López-Sánchez, E., López-Martínez, F., Escribano, J.
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3 Presymptomatic genetic diagnosis for consulters from a large Chinese family with juvenile open angle glaucoma
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