Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece

George Kitsos, Zacharias Petrou, Maria Grigoriadou, John R. Samples, Alex W. Hewitt, Haris Kokotas, Aglaia Giannoulia-Karantana, David A. Mackey, Mary Wirtz, Marilita Moschou, John P A Ioannidis, Michael B. Petersen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P <0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide.

Original languageEnglish (US)
Pages (from-to)171-178
Number of pages8
JournalClinical Ophthalmology
Volume4
Issue number1
StatePublished - 2010

Fingerprint

Greece
Mutation
Population
Primary Open Angle Glaucoma
Gene Amplification
Kaplan-Meier Estimate
Population Groups
India
Digestion
History

Keywords

  • Founder mutation
  • GLC1C
  • MYOC
  • Myocilin
  • Primary open angle glaucoma

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Kitsos, G., Petrou, Z., Grigoriadou, M., Samples, J. R., Hewitt, A. W., Kokotas, H., ... Petersen, M. B. (2010). Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece. Clinical Ophthalmology, 4(1), 171-178.

Primary open angle glaucoma due to T377M MYOC : Population mapping of a Greek founder mutation in Northwestern Greece. / Kitsos, George; Petrou, Zacharias; Grigoriadou, Maria; Samples, John R.; Hewitt, Alex W.; Kokotas, Haris; Giannoulia-Karantana, Aglaia; Mackey, David A.; Wirtz, Mary; Moschou, Marilita; Ioannidis, John P A; Petersen, Michael B.

In: Clinical Ophthalmology, Vol. 4, No. 1, 2010, p. 171-178.

Research output: Contribution to journalArticle

Kitsos, G, Petrou, Z, Grigoriadou, M, Samples, JR, Hewitt, AW, Kokotas, H, Giannoulia-Karantana, A, Mackey, DA, Wirtz, M, Moschou, M, Ioannidis, JPA & Petersen, MB 2010, 'Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece', Clinical Ophthalmology, vol. 4, no. 1, pp. 171-178.
Kitsos G, Petrou Z, Grigoriadou M, Samples JR, Hewitt AW, Kokotas H et al. Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece. Clinical Ophthalmology. 2010;4(1):171-178.
Kitsos, George ; Petrou, Zacharias ; Grigoriadou, Maria ; Samples, John R. ; Hewitt, Alex W. ; Kokotas, Haris ; Giannoulia-Karantana, Aglaia ; Mackey, David A. ; Wirtz, Mary ; Moschou, Marilita ; Ioannidis, John P A ; Petersen, Michael B. / Primary open angle glaucoma due to T377M MYOC : Population mapping of a Greek founder mutation in Northwestern Greece. In: Clinical Ophthalmology. 2010 ; Vol. 4, No. 1. pp. 171-178.
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abstract = "Background: Mutations in the MYOC gene have been shown to explain 5{\%} of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the {"}Greek{"} T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P <0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23{\%} at age 40, and reached 100{\%} at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3{\%}), in lower proportion in familial POAG cases (14.2{\%}) and seems rare in sporadic POAG cases (1.2{\%}), while no controls (0{\%}) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide.",
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T2 - Population mapping of a Greek founder mutation in Northwestern Greece

AU - Kitsos, George

AU - Petrou, Zacharias

AU - Grigoriadou, Maria

AU - Samples, John R.

AU - Hewitt, Alex W.

AU - Kokotas, Haris

AU - Giannoulia-Karantana, Aglaia

AU - Mackey, David A.

AU - Wirtz, Mary

AU - Moschou, Marilita

AU - Ioannidis, John P A

AU - Petersen, Michael B.

PY - 2010

Y1 - 2010

N2 - Background: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P <0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide.

AB - Background: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P <0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide.

KW - Founder mutation

KW - GLC1C

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KW - Myocilin

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