OBJECTIVE: To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferritinemia cataract syndrome (HHCS). METHODS: A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification. RESULTS: The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2417.70 ng/mL, reference range: 30 ~ 400 ng/ml). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c.280A>C and c.124-124+3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c.-160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS. CONCLUSION The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.
Child, Preschool ; Humans ; Male ; Cataract/genetics* ; Genetic Testing ; Mutation ; Neuronal Ceroid-Lipofuscinoses/pathology* ; Vision Disorders/genetics*

OBJECTIVETo observe the correlation of gammaD-crystallin P23T mutant with lens ultrastructure of the hereditary coralliform cataract.

METHODSComplete ophthalmologic examinations were performed before lens extraction and lens samples were studied by transmission and scanning electric microscope respectively. Protein molecular modeling was performed using SWISS-MODEL(version 2.0).

RESULTSProtein structure modeling demonstrated that the mutant caused a decrease in molecular final total energy and changes in the surface structure of gammaD-crystallin. Ultrastructure study revealed crystals deposited in lens, extensive granules dispersed in uncommon oval structure and the disorganization of lens epithelial cells.

CONCLUSIONIt is possible that the gammaD-crystallin P23T mutant is associated with abnormal crystals in lens and disorganization of lens epithelial cells.

Cataract ; congenital ; genetics ; pathology ; Female ; Humans ; Lens, Crystalline ; ultrastructure ; Male ; Pedigree ; Phenotype ; Point Mutation ; gamma-Crystallins ; genetics

BACKGROUNDCongenital cataract is a sight-threatening disease that affects about 1 - 6 cases per 10000 live births and causes 10% - 30% of all blindness in children. About 25% of all cases are due to genetic defects. We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family.

METHODSComplete ophthalmological examinations were performed prior to lens extraction. Lens samples were then studied by electron microscopy. Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing. Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2.0).

RESULTSEleven of the 23 examined individuals had congenital cataracts. Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells. The maximum two-point LOD score, 3.5 at theta = 0.1, was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD-crystallin (CRYGD). Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the gammaD protein.

CONCLUSIONSThe results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract. This study provides evidence that this same genetic defect may be associated with a different phenotype. This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract.

Cataract ; genetics ; pathology ; Female ; Genes, Dominant ; Genetic Linkage ; Humans ; Lens, Crystalline ; ultrastructure ; Male ; Microscopy, Electron ; Mutation, Missense ; gamma-Crystallins ; chemistry ; genetics

PURPOSE: To investigate the association between binocular function and vision after cataract removal and primary posterior chamber intraocular lens (PC-IOL) implantation in children with unilateral cataract and to identify visual function differences according cataract type. METHODS: Clinical records of 2- to 6-year-old patients with unilateral cataract removal and primary PC-IOL implantation were reviewed retrospectively. Visual acuity and ocular alignment were measured. Sensory fusion was assessed with the Worth 4-dot test, and stereoacuity with the Titmus stereo test. Cataracts were classified according to cause, lens opacity location, age at onset, and presence of strabismus. Clinical characteristics of patients who obtained good visual function were identified. RESULTS: Forty-seven patients were included. Among 22 (46.8%) with good vision (20/40 or better), only 6 (27.3%) achieved good binocular function (the presence of fusion and 100 seconds of arc or better of stereoacuity). Visual acuity was better in eyes with good binocular function (p=0.002). No other variables were significant for achieving good binocular function. CONCLUSIONS: The removal of unilateral cataract in a visually immature child can result in a combination of good visual acuity and binocular function. Good binocular function is closely related to good visual acuity.
Cataract/genetics/pathology ; Cataract Extraction/*methods ; Child, Preschool ; Depth Perception/*physiology ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Lens Implantation, Intraocular/*methods ; Male ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Visual Acuity/*physiology

Epalrestat is the unique aldose reductase inhibitor on the market, which was mainly used for the diabetic neuropathy. Lenses osmotic expansion could be induced by galactose to mimic the pathological process of diabetic cataract in vitro. In present study, we mainly investigated whether epalrestat possesses inhibitory effect on the lens osmotic expansion. The results indicated that epalrestat could not only markedly inhibit rat lens osmotic expansion in vitro, but also significantly reduced the high expression of the osmotic expansion-related genes such as AR and AQP1 in mRNA and protein levels. The findings may provide an important reference to epalrestat in the clinical application for the treatment of diabetic cataract.
Aldehyde Reductase ; antagonists & inhibitors ; biosynthesis ; genetics ; Animals ; Aquaporin 1 ; genetics ; metabolism ; Cataract ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Experimental ; complications ; Enzyme Inhibitors ; pharmacology ; Galactose ; antagonists & inhibitors ; Lens, Crystalline ; drug effects ; metabolism ; pathology ; Male ; Osmosis ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhodanine ; analogs & derivatives ; pharmacology ; Thiazolidines ; pharmacology