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Abstract #92558 Published in IGR 22-1
A novel proline substitution (Arg201Pro) in alpha helix 8 of TMEM98 causes autosomal dominant nanophthalmos-4, closed angle glaucoma and attenuated visual acuity
Koenighofer M; Parzefall T; Frohne A; Frei E; Waldstein SM; Mitulovic G; Schoefer C; Frei K; Lucas TExperimental Eye Research 2021; 205: 108497
Nanophthalmos-4 is a rare autosomal dominant disorder caused by two known variations in TMEM98. An Austrian Caucasian pedigree was identified suffering from nanophthalmos and late onset angle-closure glaucoma and premature loss of visual acuity. Whole exome sequencing identified segregation of a c.602G > C transversion in TMEM98 (p.Arg201Pro) as potentially causative. A protein homology model generated showed a TMEM98 structure comprising α4, α5/6, α7 and α8 antiparallel helix bundles and two predicted transmembrane domains in α1 and α7 that have been confirmed in vitro. Both p.Arg201Pro and the two missense variations representing proline insertions identified previously to cause nanophthalmos-4 (p.Ala193Pro and p.His196Pro) are located in the charge polarized helix α8 (p.183-p210). Stability of the C-terminal alpha helical structure of TMEM98 is therefore essential to prevent the development of human nanophthalmos-4. Precise molecular diagnosis could lead to the development of tailored therapies for patients with orphan ocular disease.
Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Full articleClassification:
9.1.4 Other (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
9.3.2 Chronic primary angle closure glaucoma (pupillary block) (Part of: 9 Clinical forms of glaucomas > 9.3 Primary angle closure glaucomas)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
