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. 2021 Feb;35(2):400-408.
doi: 10.1038/s41433-020-0850-z. Epub 2020 Apr 16.

The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma

Viney Gupta  1 , Bindu I Somarajan  2 , Shikha Gupta  2 , Gagandeep Kaur Walia  3 , Abhishek Singh  2 , Rayees Sofi  2 , Richard Sher Chaudhary  2 , Arundhati Sharma  4
Affiliations

The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma

Viney Gupta et al. Eye (Lond). 2021 Feb.

Abstract

Purpose: Juvenile onset primary open angle glaucoma (JOAG) is a rare disorder associated with high IOP and progressive optic neuropathy in patients diagnosed before the age of 40 years. While in some populations it has primarily an autosomal dominant pattern of inheritance, in others it occurs in a primarily sporadic form. The main aim of the study was to assess the relative prevalence of Myocilin (MYOC) mutations in familial versus sporadic cases of JOAG.

Methods: We screened 92 unrelated (sporadic) JOAG patients, and 22 affected families (70 affected members and 36 unaffected) for variations in the MYOC gene. We also analyzed the clinical features associated with these variations.

Results: Three coding sequence variants were identified as mutations causing JOAG. Four families segregated distinct mutations at Gly367Arg, and two families at Gln337Arg, while only two sporadic JOAG cases harbored MYOC mutations (Gly367Arg and Gln48His). The frequency of MYOC mutations in familial cases (27%) was significantly higher than in sporadic JOAG cases (2%); p = 0.001. A 90% penetrance for the Gly367Arg variant was seen by the age of 40 years in our patients. Characteristic allele signatures, indicative of specific founder effects, were not observed for the Gly367Arg mutation that was looked for in 12 patients among 2 geographically close families, which harbored this mutation.

Conclusion: Our data demonstrated that genetic screening for MYOC mutations should be focused toward cases with familial rather than sporadically occurring JOAG.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Pedigree of one of the four families with heterozygous Gly367Arg mutation.
a Blood samples of subjects from A to I were available for the study. Those shaded in black were diseased (glaucoma/Ocular hypertension). Those denoted with the asterisk had the mutation. Age of disease onset is denoted for each in years [brackets]. b Chromatogram showing the heterozygous Gly367Arg mutation in exon 3, of MYOC.c.1099G > A caused an amino acid change from Glycine to Arginine at codon 367.
Fig. 2
Fig. 2. Pedigree of one of the two families with homozygous Gln337Arg mutation.
a Blood samples of subjects from A to E were available for the study. Those shaded in black were diseased (glaucoma/Ocular hypertension).Those denoted with the asterisk had the mutation. Age of disease onset is denoted for each in years [brackets]. b Chromatogram showing the homozygous Gln337Arg mutation in exon 3 of MYOCc.1010A > G caused an amino acid change from Glutamine to Arginine at codon 337.
Fig. 3
Fig. 3. Pedigrees of 2 families having a common geographic location.
The Haplotype analysis of 12 members of the 2 families (a, b) with a Gly367Arg mutation Haplotypes are shown in the order of D1S2815 (1q24.4), rs534806873;c.1020G > A (intragenic), and D1S2790 (1q24.3). Disease haplotype is indicated in gray box.
See this image and copyright information in PMC

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