Myocilin Mutation N480K Leads to Early Onset Juvenile and Adult-onset Primary Open Angle Glaucoma in a Six Generation Family.

Autor:	Kader MA; Department of Glaucoma, Aravind Eye Hospital, Tirunelveli., Devarajan B; Department of Bioinformatics, Aravind Medical Research Foundation, Madurai., Vijayan S; Department of Genetics, Aravind Medical Research Foundation, Madurai., Ramakrishnan R; Department of Glaucoma, Aravind Eye Hospital, Tirunelveli., Sundaresan P; Department of Genetics, Aravind Medical Research Foundation, Madurai., Uduman MS; Department of Biostatistics, Aravind Eye Hospital, Tirunelveli., Krishnadas SR; Department of Glaucoma, Aravind Eye Hospital, Madurai., Kuppamuthu D; Department of Proteomics, Aravind Medical Research Foundation, Madurai, Tamil Nadu.
Jazyk:	angličtina
Zdroj:	Journal of glaucoma [J Glaucoma] 2024 Mar 01; Vol. 33 (3), pp. 218-224. Date of Electronic Publication: 2023 Aug 07.
DOI:	10.1097/IJG.0000000000002286
Abstrakt:	Prcis: A pathogenic autosomal dominant MYOC mutation N480K detected in 6 generations of an Indian family is primarily responsible for juvenile open angle glaucoma (JOAG) and adult-onset primary open angle glaucoma (POAG), emphasizing the importance of screening this mutation at a younger age. Purpose: To screen myocilin mutations in a large South Indian family with early-onset JOAG and adult-onset POAG. Methods: In a large South Indian family with 20 members, 8 members diagnosed as JOAG, 7 members as POAG, 4 members as JOAG suspect, and 1 member as POAG suspect were screened for myocilin ( MYOC) mutations using Sanger sequencing. Whole exome sequencing was performed on clinically suspected JOAG/POAG individuals. Results: Myocilin gene mutation N480K (c.1440C>G) was detected in 20 family members, including proband, of whom 8 were JOAG and 7 were POAG patients, 3 were JOAG suspects, and 2 were unaffected. Among the unaffected carriers, 1 was less than 5 years old, and another was 25 years old. The earliest to develop the disease was a 10-year-old child. The penetrance of the mutation was 95% over 10 years of age. This family had JOAG/POAG suspects with no N480K MYOC mutation, and they were further screened for other mutations using whole-exome sequencing. Polymorphisms CYP1B1 L432V and MYOC R76K were detected in 3 JOAG/POAG suspects, and among these 3, one had another CYP1B1 polymorphic variant R368H. The presence of the CYP1B1 polymorphism along with an MYOC polymorphic variant among the JOAG/POAG suspects needs additional studies to explore their combined role in the onset of glaucoma. Conclusions: This study reveals that MYOC mutation is primarily responsible for JOAG and adult-onset POAG in a family, emphasizing the importance of screening for this mutation at a younger age for early treatment. Competing Interests: Disclosure: The authors declare no conflict of interest. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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