Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa.

TitleMutations in POMGNT1 cause non-syndromic retinitis pigmentosa.
Publication TypeJournal Article
Year of Publication2016
AuthorsXu, M, Yamada, T, Sun, Z, Eblimit, A, Lopez, I, Wang, F, Manya, H, Xu, S, Zhao, L, Li, Y, Kimchi, A, Sharon, D, Sui, R, Endo, T, Koenekoop, RK, Chen, R
JournalHum Mol Genet
Date Published2016 Apr 15

A growing number of human diseases have been linked to defects in protein glycosylation that affects a wide range of organs. Among them, O-mannosylation is an unusual type of protein glycosylation that is largely restricted to the muscular and nerve system. Consistently, mutations in genes involved in the O-mannosylation pathway result in infantile-onset, severe developmental defects involving skeleton muscle, brain and eye, such as the muscle-eye-brain disease (MIM no. 253280). However, the functional importance of O-mannosylation in these tissues at later stages remains largely unknown. In our study, we have identified recessive mutations in POMGNT1, which encodes an essential component in O-mannosylation pathway, in three unrelated families with autosomal recessive retinitis pigmentosa (RP), but without extraocular involvement. Enzymatic assay of these mutant alleles demonstrate that they greatly reduce the POMGNT1 enzymatic activity and are likely to be hypomorphic. Immunohistochemistry shows that POMGNT1 is specifically expressed in photoreceptor basal body. Taken together, our work identifies a novel disease-causing gene for RP and indicates that proper protein O-mannosylation is not only essential for early organ development, but also important for maintaining survival and function of the highly specialized retinal cells at later stages.

Alternate JournalHum. Mol. Genet.
PubMed ID26908613
PubMed Central IDPMC4805308
Grant List1S10RR026550 / RR / NCRR NIH HHS / United States
R01EY018571 / EY / NEI NIH HHS / United States
R01EY022356 / EY / NEI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada