MAPK activation in mature cataract associated with Noonan syndrome

Abstract

Background: Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched palate, and cardiovascular malformation. Its pathological condition is thought to be due to a gain-of-function mutation in the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway. Eyelid abnormalities such as ocular hypertelorism and blepharoptosis are the most commonly observed eye complications.

Case presentation: We report a case of Noonan syndrome associated with mature cataract that required operation. A 42-year-old man was diagnosed with Noonan syndrome at the age of 1 year. He underwent an eye examination after complaining of decreased visual acuity in the right eye and was diagnosed with mature cataract, which was treated by cataract surgery. There were no intraoperative complications, and the postoperative course was uneventful. Protein analysis of lens capsule and epithelium at capsulorhexis showed MAPK cascade proteins such as ERK and p38MAPK were upregulated. An abnormality in the PTPN11 gene was also observed; a potential mechanism of cataract onset may be that opacity of the lens rapidly progressed due to abnormal activation of the Ras-MAPK signal transduction pathway.

Conclusion: This case highlights the possible association of cataract formation with MAPK cascade protein upregulation in Noonan syndrome.

Figure 1

Characteristic facial appearance. Patient presents with typical appearance such as exophthalmos and abnormal auricles.

Figure 2

Slit lamp examination on initial before and after the surgery. Initial slit lamp examination revealed (A) mature cataract in the right eye (A) and mild cataract in the left eye (B). (A) Mature cataract was observed in the right eye. Slit lamp examination after the cataract surgery in the right eye (C) and the left eye (D), showing no complication.

Figure 3

Fundus photograph before and after the surgery. (A) Fundus photograph of the right eye, but fundus could not be seen due to mature cataract. (B) Fundus photograph of the left eye, showing normal appearance. Recent fundus photograph after the cataract surgery in the right eye (C) and the left eye (D), showing normal appearances.

Figure 4

Western blot analysis of p38α MAP Kinase. Western blot of p38α MAP Kinase in lens capsule and epithelium at capsulorhexis from the patient with Noonan syndrome and senile cataract (control). Blot probed with the anti- p38α MAP Kinase antibody was detected in lens lysates from the patient with Noonan syndrome, but not from the patient with senile cataract (control).

Figure 5

Western blot analysis of phosphorylated ERK. Phosphorylated extracellular signal-regulated kinase (p-ERK1/2) expression in Western blot. (A) A representative blot. p-ERK expression in lens lysates from the patient with Noonan syndrome and senile cataract (control). Western blot analysis revealed that p-ERK expression increased in lens lysates from the patient with Noonan syndrome. (B) Semi-quantitative analysis of the band intensity showed an increase in relative p-ERK expression (values normalized to total ERK expression) in lens lysates from the patient with Noonan syndrome compared with that from control (n = 6, *P < 0.001).