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DOI: 10.1055/s-0040-1722213
Digenic Inheritance in Juvenile Open-Angle Glaucoma
Funding This study was supported by funding from the Indian Council of Medical Research (Grant Number: 5/3/8/339/2017-ITR), New Delhi, India.![](https://www.thieme-connect.de/media/10.1055-s-00029027/202302/lookinside/thumbnails/10-1055-s-0040-1722213_2000148-1.jpg)
Abstract
Juvenile open-angle glaucoma (JOAG) is an uncommon subset of primary glaucoma with an onset before the age of 40 years. In this case report, we describe the cosegregation of MYOC, p.Pro370Leu and LTBP2, p.Pro432Leu mutations in a family with JOAG. The family with autosomal dominant JOAG belonged to Northern India. The samples of proband and her parents were evaluated by whole exome sequencing. Sanger sequencing was conducted in all the study participants to check the mutations identified. Both MYOC and LTBP2 mutations were found to cosegregate in affected individuals leading to a severe JOAG phenotype, thereby suggesting a digenic inheritance of MYOC with LTBP2 in this family.
Data Availability Statement
Data supporting the findings of the study are available from the corresponding author (V.G.) on request.
Ethical Approval
All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional ethics committee and with the Declaration of Helsinki 1964 and its later amendments or comparable ethical standards.
Authors' Contributions
Study conceptualization, analysis of clinical manifestations, and manuscript preparation were done by V.G. and B.I.S. Analysis and interpretation of genetic analysis data were done by B.I.S. Analysis of clinical manifestations was done by K.M., S.G., and K.A. Manuscript revision and study supervision were done by V.G.
Publication History
Received: 04 September 2020
Accepted: 23 November 2020
Article published online:
02 February 2021
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References
- 1 Jelodari-Mamaghani S, Haji-Seyed-Javadi R, Suri F. et al. Contribution of the latent transforming growth factor-β binding protein 2 gene to etiology of primary open angle glaucoma and pseudoexfoliation syndrome. Mol Vis 2013; 19: 333-347
- 2 Saeedi O, Yousaf S, Tsai J, Palmer K, Riazuddin S, Ahmed ZM. Delineation of novel compound heterozygous variants in LTBP2 associated with juvenile open angle glaucoma. Genes (Basel) 2018; 9 (11) E527
- 3 Wiggs JL. Genetic etiologies of glaucoma. Arch Ophthalmol 2007; 125 (01) 30-37
- 4 Craig JE, Baird PN, Healey DL. et al. Evidence for genetic heterogeneity within eight glaucoma families, with the GLC1A Gln368STOP mutation being an important phenotypic modifier. Ophthalmology 2001; 108 (09) 1607-1620
- 5 Fingert JH, Héon E, Liebmann JM. et al. Analysis of myocilin mutations in 1703 glaucoma patients from five different populations. Hum Mol Genet 1999; 8 (05) 899-905
- 6 Gupta V, Somarajan BI, Gupta S. et al. The inheritance of juvenile onset primary open angle glaucoma. Clin Genet 2017; 92 (02) 134-142
- 7 Gupta V, Somarajan BI, Gupta S. et al. The mutational spectrum of myocilin gene among familial versus sporadic cases of juvenile onset open angle glaucoma. Eye (Lond) 2020
- 8 Hogewind BF, Gaplovska-Kysela K, Theelen T. et al. Identification and functional characterization of a novel MYOC mutation in two primary open angle glaucoma families from The Netherlands. Mol Vis 2007; 13: 1793-1801
- 9 Iliev ME, Bodmer S, Gallati S. et al. Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation. Eye (Lond) 2008; 22 (07) 880-888
- 10 Vincent AL, Billingsley G, Buys Y. et al. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet 2002; 70 (02) 448-460
- 11 Mukhopadhyay A, Acharya M, Mukherjee S. et al. Mutations in MYOC gene of Indian primary open angle glaucoma patients. Mol Vis 2002; 8: 442-448
- 12 Hewitt AW, Mackey DA, Craig JE. Myocilin allele-specific glaucoma phenotype database. Hum Mutat 2008; 29 (02) 207-211
- 13 Adam MF, Belmouden A, Binisti P. 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 (12) 2091-2097
- 14 Suzuki Y, Shirato S, Taniguchi F, Ohara K, Nishimaki K, Ohta S. Mutations in the TIGR gene in familial primary open-angle glaucoma in Japan. Am J Hum Genet 1997; 61 (05) 1202-1204
- 15 Hassan MS, Shaalan AA, Dessouky MI, Abdelnaiem AE, ElHefnawi M. Evaluation of computational techniques for predicting non-synonymous single nucleotide variants pathogenicity. Genomics 2019; 111 (04) 869-882
- 16 Raimondi D, Gazzo AM, Rooman M, Lenaerts T, Vranken WF. Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects. Bioinformatics 2016; 32 (12) 1797-1804
- 17 Ali M, McKibbin M, Booth A. et al. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet 2009; 84 (05) 664-671
- 18 Désir J, Sznajer Y, Depasse F. et al. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Eur J Hum Genet 2010; 18 (07) 761-767
- 19 Khan AO, Aldahmesh MA, Alkuraya FS. Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations. Mol Vis 2011; 17: 2570-2579
- 20 Gazzo AM, Daneels D, Cilia E. et al. DIDA: A curated and annotated digenic diseases database. Nucleic Acids Res 2016; 44 (D1): D900-D907