A novel PAX3 mutation in a Korean patient with Waardenburg syndrome type 1 and unilateral branch retinal vein and artery occlusion: a case report

Abstract

BackgroundWaardenburg syndrome (WS) is a very rare genetic disorder affecting the neural crest cells. Coexistence of branch retinal vein occlusion (BRVO) and branch retinal artery occlusion (BRAO) in the same eye is also a rare finding. Here we report a case of WS type 1 that was confirmed by a novel mutation with the finding of unilateral BRVO and BRAO.Case presentationA 36-year-old, white-haired Korean man presented with a complaint of loss of vision in the inferior visual field of his right eye and hearing loss. He had telecanthus with a medial eyebrow and a hypochromic left iris. Funduscopy showed an ischemic change at the posterior pole in the right eye with sparing of the foveal center as well as retinal hemorrhages and white patches along the superotemporal arcade. Fundus angiography revealed the presence of both BRVO and BRAO, and optical coherence tomography showed thickening and opacification of the retinal layers corresponding to the ischemic area. A blood workup revealed hyperhomocysteinemia and the presence of antiphospholipid antibodies; both are suggestive as the cause of the BRVO and BRAO. Single nucleotide polymorphism analysis confirmed a novel PAX3 mutation at 2q35 (c.91–95 ACTCC deletion causing a frameshift). These findings confirmed a diagnosis of WS type 1.ConclusionsWS is a heterogeneous inherited disorder of the neural crest cells that causes pigment abnormalities and sensorineural hearing loss. This is the first report of unilateral BRVO and BRAO in a patient with WS. Furthermore, the PAX3 mutation identified in this patient has not been reported previously.

Single-Cell RNA Sequencing Reveals Molecular Features of Heterogeneity in the Murine Retinal Pigment Epithelium

“…By contrast, it is likely that choroidal melanocytes rely on Pax3 rather than Pax6 for development and/or melanogenesis, similar to neural crest-derived melanocytes in the skin and hair follicles [ 64 , 65 , 66 ]. This premise is supported by the labeling of choroidal but not RPE cells using a Pax3 -green fluorescent protein reporter in mice [ 67 ], by the identification of Pax3 but not Pax6 in the transcriptional signature of murine choroidal melanocytes [ 68 , 69 ], and by reports that PAX3 mutations in patients with Waardenburg syndrome cause choroidal hypopigmentation without affecting RPE pigmentation [ 70 , 71 , 72 ]. Pax3 was not identified among C1 marker genes ( Data S1 ).…”

Two novel mutations of PAX3 and SOX10 were characterized as genetic causes of Waardenburg Syndrome

“…The first proband in family I was diagnosed as WS I, based on additional symptoms of dystopia canthorum and phenotypes Recently, many novel PAX3 mutations were reported, such as c.91-95de1ACTCC, c.808C>G, and c.117C>A (Choi, Choi, & Lee, 2018;Li et al, 2019;Ma, Lin, et al, 2019). To verify the clinical diagnosis in proband I, genetic screening of PAX3 was performed and c.372-373delGA (p.N125fs) was identified.…”

<p>Combined Central Retinal Vein And Artery Occlusion In A Patient With Elevated Level Of Factor VIII: A Case Report</p>

“…The etiologies may be mechanical compression of the optic nerve, such as inadvertent retrobulbar injection in the optic nerve sheath, optic nerve inflammation from systemic disease or orbital inflammatory pseudotumor 8–10. Additionally, systemic disorders may also cause combined RVO and RAO, such as protein C deficiency, systemic lupus erythematous, antiphospholipid syndrome, and PAX3 mutation with Waardenburg syndrome type 1 11–13…”