Disruption of PIKFYVE causes congenital cataract in human and zebrafish

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. However, the molecular mechanisms underlying the pathogenesis of congenital cataract remain incompletely defined. Through whole-exome sequencing of a Chinese family with congenital cataract, we identified a potential pathological variant (p.G1943E) in PIKFYVE, which is located in the PIP kinase domain of the PIKFYVE protein. We demonstrated that heterozygous/homozygous disruption of PIKFYVE kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKFYVE activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and pinpointed the potential application of Baf-A1 for the treatment of congenital cataract caused by PIKFYVE deficiency.

Congenital Cataract Surgery: A Retrospective Analysis of 62 Patients in a Developing Country

Purpose. This study was aimed at describing our experience in congenital cataract surgery in a developing Country. Methods. A retrospective study was conducted in Amman, Jordan. The patients who were diagnosed with congenital cataract and underwent the surgery were included in the study. It was decided to use an intraocular lens if the corneal diameter was more than 10 millimeters. Results. The findings revealed that around 13 of the patients did not have any visual axis opacification, indicating that they were aphakic. Visual axis opacification was seen in 8 out of the total sample of participants. Eleven patients with obvious opacification of the visual axis were found to be pseudophakic after at least two procedures and were thus cleared. It was necessary to do a second surgery to rectify the visual axis opacification induced by pseudophakia, which was putting the patient’s ability to recuperate at danger. Three of them (or 12 percent) exhibited visual axis opacification, which is a rare occurrence. The intraocular lenses used in the remaining 24 patients were constructed of hydrophilic plastic. Conclusion. Patients are less prone to have visual axis opacification while implanted by hydrophobic intraocular lenses is something they should consider.

Defect of LSS Disrupts Lens Development in Cataractogenesis

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

Study on the enlargement index of femtosecond laser-assisted capsulorhexis in 2–6-year-old patients with congenital cataract

Background To identify the capsule enlargement index after femtosecond laser-assisted anterior capsulorhexis in 2–6-year-old children who underwent congenital cataract surgery. Methods In this prospective case series study, femtosecond laser-assisted anterior capsulorhexis was performed in patients with congenital cataract, aged 2–6 years. The actual achieved capsulorhexis diameters were measured with Digimizer version 4.2.6. Correlation coefficient (r) and multiple linear regression analysis were used to evaluate the variables that could potentially influence anterior capsulorhexis enlargement index (E). Results This prospective study enrolled 28 eyes of 22 patients with congenital cataract. The mean age of the patients at surgery was 4.67 years ±1.54 (standard deviation [SD]). “E” of the 28 cases was 1.211 ± 0.039 (SD). Correlation analysis showed that “E” correlated significantly with the anterior chamber depth (ACD) (r = − 0.469, p = 0.021) and axial length (AL) (r = 0.452, p = 0.027). The following formula was developed by using multivariable linear regression analysis: Predicted E = 1.177–0.052 × ACD + 0.009 × AL, R2 = 0.346 (F = 4.396, p = 0.046). Conclusions The anterior capsulorhexis enlargement index and its calculation formula could help to set up an accurate programmed capsulorhexis diameter for femtosecond laser-assisted congenital cataract surgery in children aged 2–6 years. Thus, an appropriate actual capsulorhexis diameter could be achieved.

Spiroplasma species as a rare cause of congenital cataract and uveitis: a case series

Background To date, only four cases of ocular spiroplasma infection have been reported in the entire ophthalmic literature. We add two more cases to raise awareness of this sight-threatening congenital disease that manifests as cataract with ocular inflammation. Case presentation Both infants were referred for cataracts associated with ocular inflammation. Case 1, a 3-week-old neonate presented with unilateral cataract, ocular inflammation and elevated intraocular pressure. Case 2 was a 3-month-old infant with bilateral cataract and panuveitis. Lensectomies with or without vitrectomy and subsequent analyses of the specimens were performed. Transmission electron microscopy and multiplex polymerase chain reaction or 16 s rRNA gene polymerase chain reaction revealed spiroplasma species. Conclusions Spiroplasma as a very rare cause for congenital cataract might be underdiagnosed. We recommend performing polymerase chain reaction to probe for spiroplasma species in congenital cataracts with an inflammatory component.

Novel SOX2 Mutation in Autosomal Dominant Cataract-Microcornea Syndrome

Background: Congenital cataract-microcornea syndrome (CCMC) is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although several causative genes have been reported in patients with CCMC, the genetic etiology of CCMC is yet to be clearly understood. Purpose: To unravel the genetic cause of autosomal dominant family with CCMC.Methods: All patients and available family members underwent a comprehensive ophthalmologic clinical examination in the hospital by expert ophthalmologists and carried out to clinically diagnosis. All the patients were screened by whole-exome sequencing and then validated using co-segregation by Sanger sequencing. Results: Four CCMC patients from a Chinese family, and five unaffected family members were enrolled in this study. Using whole-exome sequencing, missense mutation c.295G>T (p.a99s, NM_003106.4) in the SOX2 gene was identified and validated by segregation analysis. In addition, this missense mutation was predicted to be damaging by multiple predictive tools. Variant p.Ala99Ser was located in a conservation high mobility group (HMG)-box domain in SOX2 protein, with a potential pathogenic impact of p.Ala99Ser on protein level.Conclusions: A novel missense mutation (c.295G>T, p.Ala99Ser) in the SOX2 gene was found in this Han Chinese family with congenital cataract and microcornea. Our study firstly determined that mutations in SOX2 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder. This result expands the mutation spectrum of SOX2 and provides useful information to study the molecular pathogenesis of CCMC.

Comprehensive Management of Congenital Cataract in Dizygotic Twin Babies

Introduction: One of the leading causes of infant blindness is cataract. The prevalence of congenital cataract has been estimated in the range between 1 and 15 per 10.000 children globally. Congenital cataract in twin babies is a rare case. This case will report the outcome of comprehensive management of congenital cataract in dizygotic twin babies. Case presentation: Eight months old dizygotic twin babies came to our clinic with the primary complaint of whitish appearance in the pupil of both eyes since birth. They were born aterm with cesarean delivery. The birth weight was 2.700 g and 3.100 g respectively. They were the fourth and fifth children in the family. There was no family history of congenital cataract. The visual acuity of both eyes was positive response to light stimuli. The cataract was bilateral and dense on both babies. Fundus reflex and TORCH examinations were negative. Ultrasonography (USG) of the retina was normal on both babies. Conclusions: Isolated congenital cataract in twin babies is an unusual condition that should be treated comprehensively. Congenital cataract may cause deprivation amblyopia, refractive amblyopia, and permanent vision impairment. Early diagnosis and quick treatment, such as surgical timing and visual rehabilitation, are critical to perform successful management. Comprehensive care is required to monitor the visual result of cataract surgery.