Characterization of a p.R76H mutation in Cx50 identified in a Chinese family with congenital nuclear cataract.

BACKGROUND/PURPOSE: A three-generation Chinese family with autosomal dominant congenital nuclear cataract was recruited. This study aimed to identify the disease-causing gene for nuclear cataract with functional dissections of the identified mutant. METHODS: Detailed clinical data and family history were recorded. Candidate gene sequencing was performed to identify the disease-causing mutation. Recombinant connexin50 (Cx50) wild type and mutant constructs were synthesized. Triton X-100 solubility and subcellular localization of the recombinant Cx50 proteins were analyzed in HeLa cells. Apoptosis was assayed as the percentage of fragmented nuclei in transfected cells. RESULTS: All affected individuals in the family displayed clear phenotypes of dense nuclear cataracts. A c.227 G > A variation was found in the coding region of Cx50, which arginine residue at position 76 was substituted by histidine (p.R76H). This mutation was co-segregated with the disease in the family, and was not observed in 110 unrelated Chinese controls. No statistically significant differences were found in the Triton X-100 solubility and apoptosis rate between wild type and mutant Cx50 in HeLa cells. However, Cx50 mutant was unable to form gap junctional plaques between adjacent cells as the wild type proteins did. CONCLUSION: This study identified a novel cataract phenotype caused by the p.R76H mutation in Cx50, providing evidence of further phenotypic heterogeneity associated with this mutation. Functional analysis showed that the mutation affected the formation of gap junction channels and led to opacity in the lens.

[Analysis of the Related Risk Factors of Cerebral AVM Hemorrhage and the Relationship Between EPCs and SDF-1 in Brain AVM].

OBJECTIVE: To explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages. METHODS: A retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed. RESULTS: The size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages ( P<0.05). There was no significant difference in EPCs between cerebral hemorrhage group and non-hemorrhage group ( P>0.05). CONCLUSION: Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM.

Randomized controlled trial on the efficacy and safety of autologous serum eye drops in dry eye syndrome.

BACKGROUND: Autologous serum eye drops (ASEDs), a novel treatment derived from blood serum, have emerged as a groundbreaking solution for managing dry eye syndrome (DES). These drops have shown significant promise in relieving the distressing symptoms of DES. This study aimed to evaluate the safety and effectiveness of ASEDs compared to traditional treatments, which often prove inadequate or result in unwanted side effects, particularly in individuals with moderate-to-severe DES. AIM: To evaluate whether ASEDs are safer and more effective than conventional artificial tears in the treatment of moderate-to-severe DES. METHODS: This multi-centered randomized controlled trial included 240 patients with moderate-to-severe DES from three ophthalmology clinics in China. They were randomly assigned to receive either ASEDs or artificial tears for 12 wk. The primary outcome was the change in the ocular surface disease index (OSDI) score, with secondary outcomes including tear break-up time (TBUT), Schirmer I test, corneal fluorescein staining (CFS), and conjunctival impression cytology (CIC). Statistics analysis was performed using an analysis of covariance with adjustments made for baseline values. RESULTS: Our findings revealed that both ASEDs and artificial tears significantly improved the OSDI score, TBUT, Schirmer I test, CFS, and CIC from baseline to week 12. The ASEDs group showed significantly greater improvement in all these measures than the artificial tears group (all P values < 0.05). The average difference in the OSDI score between the two cohorts was -10.3 (95% confidence interval: -13.6 to -7.0), indicating a substantial improvement in the ASEDs group. The occurrence of adverse events was comparable between cohorts, with no reports of severe adverse events. CONCLUSION: ASEDs are more effective and safer than artificial tears for mitigating symptoms of moderate-to-severe DES. ASEDs could be an alternative/supplementary therapy for patients with DES less responsive to traditional treatments.

A novel p.F206I mutation in Cx46 associated with autosomal dominant congenital cataract.

PURPOSE: To identify the genetic defect in a Chinese family with bilateral congenital cataract. METHODS: A three-generation family was recruited in this study. Detailed family history and clinical data were recorded. Ten candidate genes were screened for causative mutations. Direct sequencing was performed to analyze the cosegregation of the genotype with the disease phenotype. RESULTS: Affected individuals presented embryonal nuclear opacities in the lens. Sequencing of the candidate genes showed a heterozygous c. 616T>A variation in the connexin 46 (Cx46) gene, which resulted in the replacement of a highly conserved phenylalanine by isoleucine at codon 206 (p. F206I). This mutation co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched controls. CONCLUSIONS: We report a novel mutation (p.F206I) in the fourth transmembrane domain of connexin 46. These findings thus expand the mutation spectrum of Cx46 in association with congenital cataract.

[Detection of differentially expressed lumican gene mRNA level in scleral tissue in human eye].

OBJECTIVE: To identify differentially expressed lumican in scleral tissue of eyes with primary open-angle glaucoma (POAG) and high myopia (HM). METHODS: Total RNA was isolated from scleral tissue of cadaveric eyes derived from normal donors, patient's eyes with diagnosed glaucoma and high myopia who accepted trabeculectomy. RNA was amplified, RT-PCR was used to measure the levels of mRNA. The ratio of the electrophoresis strips'gray scale values of the ß-actin over the lumican gene was obtained for ANOVA analysis. RESULTS: ß-actin/LUM of normal eye was significantly higher than that of POAG and POAG + HM eyes (P < 0.01), but there was no significant difference between POAG and POAG + HM eyes (P > 0.05). CONCLUSIONS: Differentially expressed lumican between POAG and control groups identified in this study have not been previously investigated for their role in the pathogenesis of POAG and thus are novel factors for further study of the mechanism of the disease and for their possible use as diagnostic markers.

Therapeutic potential of pupilloplasty combined with phacomulsification and intraocular lens implantation against uveitis-induced cataract.

AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation (PPI) in uveitis-induced cataract. METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin (HE) staining was performed to reveal the histopathological changes of iris tissues. RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity (BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1wk. During the follow-up of 5-10y, no recurrence of uveitis was found in 27 cases (96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma (all samples), pigment cell hyperplasia in pigment epithelium (n=9) and stroma (n=19), inflammatory cell infiltration in iris (n=7), and neovascularization in iris surface (n=2). CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality (glaucoma) and inflammation (active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.

Spaceflight-associated neuro-ocular syndrome: a review of potential pathogenesis and intervention.

With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition "spaceflight-associated neuro-ocular syndrome" (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.

A novel mutation in CRYBB1 associated with congenital cataract-microcornea syndrome: the p.Ser129Arg mutation destabilizes the ßB1/ßA3-crystallin heteromer but not the ßB1-crystallin homomer.

Congenital cataract-microcornea syndrome (CCMC) is a clinically and genetically heterogeneous condition characterized by lens opacities and microcornea. It appears as a distinct phenotype of heritable congenital cataract. Here we report a large Chinese family with autosomal dominant congenital cataract and microcornea. Evidence for linkage was detected at marker D22S1167 (LOD score [Z]=4.49, recombination fraction [θ]=0.0), which closely flanks the â-crystallin gene cluster locus. Direct sequencing of the candidate âB1-crystallin gene (CRYBB1) revealed a c.387C>A transversion in exon 4, which cosegregated with the disease in the family and resulted in the substitution of serine by arginine at codon 129 (p.Ser129Arg). A comparison of the biophysical properties of the recombinant ß-crystallins revealed that the mutation impaired the structures of both ßB1-crystallin homomer and ßB1/ßA3-crystallin heteromer. More importantly, the mutation significantly decreased the thermal stability of ßB1/ßA3-crystallin but not ßB1-crystallin. These findings highlight the importance of protein-protein interactions among ß-crystallins in maintaining lens transparency, and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCMC.

A novel mutation in MIP associated with congenital nuclear cataract in a Chinese family.

PURPOSE: To identify the underlying genetic defect in a Chinese family affected with autosomal dominant congenital nuclear cataract. METHODS: A four-generation Chinese family with inherited nuclear cataract phenotype was recruited. Detailed family history and clinical data were recorded. All reported nuclear cataract-related candidate genes were screened for causative mutations by direct DNA sequencing. Effects of amino acid changes on the structure and function of protein were predicted by bioinformatics analysis. RESULTS: All affected individuals in this family showed nuclear cataracts. Sequencing of the candidate genes revealed a heterozygous c.559C>T change in the coding region of the major intrinsic protein (MIP), which caused a substitution of highly conserved arginine by cysteine at codon 187 (p.R187C). This mutation co-segregated with all affected individuals and was not observed in unaffected family members or 110 ethnically matched controls. Bioinformatics analysis showed that the mutation was predicted to affect the function and secondary structure of MIP protein. CONCLUSIONS: This study identified a novel disease-causing mutation p.R187C in MIP in a Chinese cataract family, expanding the mutation spectrum of MIP causing congenital cataract.

The association of a single nucleotide polymorphism in the promoter region of the LAMA1 gene with susceptibility to Chinese high myopia.

PURPOSE: High myopia is a severe hereditary ocular disease leading to blindness. LAMA1 (alpha subunit of laminin) is a promising candidate gene for high myopia present in the MYP2 (myopia 2) region. The purpose of this study was to determine if high myopia is associated with single nucleotide polymorphism (SNP) variants in LAMA1 in Chinese subjects. METHODS: Ninety-seven Chinese subjects with high myopia and ethnically and sexually matched 103 normal controls were enrolled. Genomic DNA was prepared from peripheral blood. The 5 SNPs of LAMA1 were analyzed using PCR and SNaPshot. Allele frequencies were tested for Hardy-Weinberg disequilibrium. The genotype and allele frequencies were evaluated using the χ(2) tests or the Fisher exact tests. RESULTS: One of the 5 SNPs showed a significant difference between patients and control subjects (rs2089760: p(genotype)=0.005, p(allel)=0.003). There were no statistically significant differences between patients and control subjects for the other four SNPs: rs566655, rs11664063, rs607230, and rs3810046. CONCLUSIONS: Our results indicate that the polymorphism of rs2089760, located in the promoter region of LAMA1, may be associated with high myopia in the Chinese population and should be investigated further.

Spontaneous dislocation of a Verisyse phakic intraocular lens with severe corneal endothelial cell loss.

PURPOSE: To report a case of spontaneous dislocation of a Verisyse phakic intraocular lens (PIOL) with severe corneal endothelial cell loss. METHODS: A 29-year-old woman with no history of trauma presented with complaint of blurred vision in the right eye of 5 months' duration. History included uneventful implantation of a PIOL bilaterally to correct high myopia in January 2007. RESULTS: Visual acuity was 20/100, central endothelial cell density had decreased to 592/mm(2), central corneal pachymetry was 634 microm. The PIOL dislocated temporally and was removed without any lens implanted again. Three months postoperatively, her best-corrected visual acuity was 20/60. CONCLUSIONS: A correct fixation with sufficient folded iris inside the claw and long-term follow-up are important for patients with implanted PIOL, and the long-term effects on endothelial cell density in this patient remain to be seen.

[Progress in pathogenic genes and their functions of congenital cataract].

Congenital cataract is the common cause of visual disability in children. Inherited isolated (non-syndromic) cataract represents one third of cases. Currently, at least 22 specific genes associated with isolated inherited cataract have been identified: ten crystallin genes: CRYAA, CRYAB, CRYBA1/A3, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS; 4 membrane protein genes: GJA3, GJA8, MIP, LIM2; three growth and transcription factor genes: PITX3, MAF, HSF4; two cytoskeletal protein gene: BSFP1, BSFP2; chromatin modifying protein-4B gene: CHMP4B, EPHA2 and NHS, it is likely that more genes remain to be discovered. Some of the genes have been studied for their function by expression in cells or/and by knock-out animal models. The increasing availability of more detailed information about their functions makes it possible to understand the pathophysiology of congenital cataracts.

[Evaluation of intraocular lens power after keratorefractive surgery by IOLMaster].

OBJECTIVE: To study the accuracy of different formulas predicting intraocular lens (IOL) power after excimer laser keratorefractive surgery in order to calculate the diopter of IOL accurately in the clinical practice. METHODS: One hundred and eleven cases (222 eyes) were collected in this study and were divided into two groups (A and B) according to their axial length. Fifty-nine cases (118 eyes) with axial lengths of 24-26 mm were taken as group A, and 52 cases (104 eyes) with axial length of more than 26 mm were taken as group B. All of the subjects enrolled in this study were examined by the IOL-Master before and after LASIK, including the axial length, corneal curvature, anterior chamber depth (ACD), and the IOL power which was predicted by the SRK-II, SRK/T, Hoffer Q, Holladay, Haigis-L formulas and the Clinical History method offered by IOL-Master. The significance of the differences was analysed by using student's t-test. RESULTS: The corneal curvature after LASIK decreased significantly (t = 12.10, P < 0.01); the length of axis and ACD also decreased but had no significant differences as compared with pre-operation. The IOL powers of the two groups offered by the Haigis-L formula were significantly more than that offered by other formulas (t = 0.54, 1.21, P < 0.01). The difference between the Haigis and Haigis-L formulas was the smallest, and the difference between the SRK-II and Haigis-L formula was the greatest. The IOL powers offered by the clinical history method were higher than that offered by these formulas; the differences were significant in both group A and group B, except the group A in SRK-II (t = 0.00, -1.73, 0.00, P < 0.01). The IOL powers offered by Haigis-L were greater than that from the clinical history method or other formulas and showed significant differences except that between Haigis-L and CH-Haigis or CH-Haigis-L formula (P < 0.01). CONCLUSIONS: Taking into consideration the difference of IOL power offered by Haigis-L formula as compared with other current formulas, evaluation by IOL-Master will be helpful for improving the accuracy of IOL power prediction for the cataract eyes receiving corneal refractive surgery. However, the accuracy of the Haigis-L formula for eyes after corneal refractive surgery still requires to be confirmed by a further series of clinic data.

Recurrent PAX 6 mutation in a Chinese family with congenital aniridia, progressive cataracts and mental retardation.

BACKGROUND: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation. METHODS: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples. RESULTS: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family. CONCLUSION: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

[Quality of vision in patients with aspherical diffractive multifocal intraocular lens implantation].

OBJECTIVE: To evaluate the visual performance of patients with Tecnis ZM900 aspherical diffractive multifocal intraocular lens (MIOL) as compared with aspherical monofocal intraocular lens (IOL). METHODS: A prospective nonrandomized controlled study was conducted. Consecutively 114 senile cataract patients (114 eyes) received phacoemulsification and IOL implantation, 57 patients (57 eyes) were implanted Tecnis ZM900 MIOL (multifocal group) and 57 patients (57 eyes) were implanted aspherical Tecnis ZA9003 IOL (monofocal group). All patients were assessed at 3 months postoperatively: uncorrected and best corrected visual acuities for distance and near, distance corrected near visual acuity, higher-order aberrations of IOL, modulation transfer function, contrast visual acuity at different contrast levels and different distance (40 cm, 63 cm and 100 cm) and pseudoaccommodation. Patient satisfaction (spectacle independence, photic phenomena and overall satisfaction) was assessed by a questionnaire. RESULTS: At 3 months post-operation, both uncorrected near visual acuity and distance corrected near visual acuity were significantly better in multifocal group than monofocal group (t = - 7.62, - 9.89, P < 0.05). The accommodative range was (4.74 +/- 1.05) D in multifocal group and (1.65 +/- 0.68) D in monofocal group (P < 0.01). There was no statistically significantly difference between the two groups in IOL higher-order aberration with different pupil sizes (3 mm vs 5 mm). At the distance of 40 cm and 63 cm, visual acuity scores were higher in multifocal group than in monofocal group (P < 0.01). Modulation transfer function was similar in the two groups and there was no statistically significantly difference. The spectacle independence was 85.9% in multifocal group versus 24.6% in the monofocal group (chi2 = 43.46, P < 0.05). CONCLUSION: Compared with aspherical monofocal IOL, the Tecnis ZM900 aspherical diffractive MIOL not only provided certain pseudoaccommodation with a better useful near visual acuity, but also provided a better quality of vision, resulting in higher levels of spectacle independence and patient satisfaction.

A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts.

PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital lamellar cataracts and demonstrate the functional analysis with biosoftware of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinations were performed on family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated by using the Linkage Software after genotyping. A mutation was detected by using gene-specific primers in direct sequencing. Wild type and mutant proteins were analyzed with Online Bio-Software. RESULTS: Affected members of this family had lamellar cataracts. Linkage analysis was obtained at markers D3S2322 (LOD score [Z]=7.22, recombination fraction [theta]=0.0) and D3S1541 (Z=5.42, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the beaded filament structural protein 2 (BFSP2) gene revealed a G>A transversion in exon 5, which caused a conservative substitution of Arg to His at codon 339 (P.R339H). This mutation cosegregated with the disease phenotype in all affected individuals and was not observed in the unaffected family members or in 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Arg339. Data generated with Online Bio-Software revealed that the mutation altered the protein's hydrophobicity, hydrophobic moment, and chaperone and regulation activities. CONCLUSIONS: This is the first reported case of a congenital lamellar cataract phenotype associated with the mutation of Arg339His (P.R339H) in BFSP2. It highlights the physiologic importance of the beaded filament protein and demonstrates a possible mechanism of action for the mutant gene.

Nonsense mutation in the CRYBB2 gene causing autosomal dominant progressive polymorphic congenital coronary cataracts.

PURPOSE: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail. METHODS: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing high-performance liquid chromatography (DHPLC). RESULTS: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [theta]=0.0) and D22S1167 (Z=1.20, theta=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the betaB-crystallin gene (CRYBB2) revealed a C --> T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals. CONCLUSIONS: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.

[Cortical plasticity in blind individual].

The cognitive mechanisms and functional brain imaging research on blind individuals provide special information for exploring the plasticity of the developing human brain. This paper focuses on five aspects of recent progress in this field: (1) the behavior compensation of the blind; (2) the influence of early visual deprivation and later visual deprivation on cross-modal reorganization; (3) the relationship between the complexity of task requirement and cross-modal reorganization; (4) the relationship between the sensitive periods of the visual system and the time course of cross-modal reorganization; (5) the neural mechanisms of cross-modal reorganization. These findings contribute greatly to the theoretical basis of the rehabilitation of individuals with perceptual deficits.

Mutation Analysis of Families with Autosomal Dominant Congenital Cataract: A Recurrent Mutation in the CRYBA1/A3 Gene Causing Congenital Nuclear Cataract.

PURPOSE: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype-phenotype correlations in Chinese families with congenital cataract. METHODS: Family history and clinical data of 47 unrelated families with autosomal dominant congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied to identify the causative mutation. Haplotypes were constructed using closely linked microsatellite markers and intragenic single-nucleotide polymorphisms (SNPs) to compare the affected haplotype in three families. RESULTS: Nuclear cataract was the most common type of ADCC in Chinese families, accounting for 42.6% (20/47). A recurrent CRYBA1/A3 deletion mutation (ΔG91) was identified in three families (6.4%) with nonprogressive nuclear congenital cataract. Different haplotypes segregated with the mutation in each family. CONCLUSIONS: A recurrent ΔG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese families with autosomal dominant nuclear cataracts and most likely represents a mutational hot spot, which underscores the relations between nonprogressive nuclear cataract and CRYBA1/A3.

A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract.

BACKGROUND: Congenital cataract is a highly heterogeneous disorder at both the genetic and phenotypic levels. This study was conducted to identify disease locus for autosomal dominant congenital cataracts in a four generation Chinese family. METHODS: Family history and clinical data were recorded. All the members were genotyped with microsatellite markers which are close to the known genetic loci for autosomal congenital cataracts. Two-point Lod scores were obtained using the MLINK of the LINKAGE program package (ver 5.1). Candidate genes were amplified by polymerase chain reaction (PCR) and direct cycle sequencing. RESULTS: The maximum Lod score of Zmax-2.11 was obtained with three microsatellite markers D22S258, D22S315, and D22S1163 at recombination fraction theta=0. Haplotype analysis showed that the disease gene was localized to a 18.5 Mbp region on chromosome 22 flanked by markers D22S1174 and D22S270, spanning the beta-crystallin gene cluster. A c.752T-->C mutation in exon 6 of CRYBB1 gene, which resulted in a heterozygous S228P mutation in predicted protein, was found to cosegregate with cataract in the family. CONCLUSIONS: This study identified a novel mutation in CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract. These results provide strong evidence that CRYBB1 is a pathogenic gene for congenital cataract.