A HU-like protein is required for full virulence in Xanthomonas campestris pv. campestris.

Bacteria harbour several abundant small DNA-binding proteins known as nucleoid-associated proteins (NAPs) that contribute to the structure of the bacterial nucleoid as well as to gene regulation. Although the function of NAPs as global transcriptional regulators has been comprehensively studied in the model organism Escherichia coli, their regulatory functions in other bacteria remain relatively poorly understood. Xanthomonas campestris pv. campestris (Xcc) is a gram-negative bacterium that causes black rot disease in almost all members of the crucifer family. In previous work, we demonstrated that a Fis homologue protein, which we named Fis-like protein (Flp), contributes to the regulation of virulence, type III secretion, and a series of other phenotypes in Xcc. Here we have examined the role of XC_1355, which is predicted to encode a DNA-binding protein belonging to the HU family herein named HU-like protein (Hlp). We show that mutation of XC_1355 in Xcc reduces the virulence, extracellular polysaccharide production, and cell motility, but has no effect on the production of extracellular enzymes and induction of the hypersensitive response. These data together with transcriptome analysis indicate that hlp is a previously uncharacterized gene involved in virulence that has partially overlapping and complementary functions with flp in Xcc, although the two regulators have opposite effects on the expression of genes involved in type III secretion. The findings add to our understanding of the complex regulatory pathways that act to regulate virulence in Xcc.

PilG and PilH antagonistically control flagellum-dependent and pili-dependent motility in the phytopathogen Xanthomonas campestris pv. campestris.

BACKGROUND: The virulence of the plant pathogen Xanthomonas campestris pv. campestris (Xcc) involves the coordinate expression of many virulence factors, including surface appendages flagellum and type IV pili, which are required for pathogenesis and the colonization of host tissues. Despite many insights gained on the structure and functions played by flagellum and pili in motility, biofilm formation, surface attachment and interactions with bacteriophages, we know little about how these appendages are regulated in Xcc. RESULTS: Here we present evidence demonstrating the role of two single domain response regulators PilG and PilH in the antagonistic control of flagellum-dependent (swimming) and pili-dependent (swarming) motility. Using informative mutagenesis, we reveal PilG positively regulates swimming motility while and negatively regulating swarming motility. Conversely, PilH negatively regulates swimming behaviour while and positively regulating swarming motility. By transcriptome analyses (RNA-seq and RT-PCR) we confirm these observations as PilG is shown to upregulate many genes involved chemotaxis and flagellar biosynthesis but these similar genes were downregulated by PilH. Co-immunoprecipitation, bacterial two-hybrid and pull-down analyses showed that PilH and PilG were able to interact with district subsets of proteins that potentially account for their regulatory impact. Additionally, we present evidence, using mutagenesis that PilG and PilH are involved in other cellular processes, including chemotaxis and virulence. CONCLUSIONS: Taken together, we demonstrate that for the conditions tested PilG and PilH have inverse regulatory effects on flagellum-dependent and pili-dependent motility in Xcc and that this regulatory impact depends on these proteins influences on genes/proteins involved in flagellar biosynthesis and pilus assembly.

Flp, a Fis-like protein, contributes to the regulation of type III secretion and virulence processes in the phytopathogen Xanthomonas campestris pv. campestris.

The ability of the plant pathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on its ability to adapt quickly to the host environment during infection. Like most bacterial pathogens, Xcc has evolved complex regulatory networks that ensure expression and regulation of their virulence genes. Here, we describe the identification and characterization of a Fis-like protein (named Flp), which plays an important role in virulence and type III secretion system (T3SS) gene expression in Xcc. Deletion of flp caused reduced virulence and hypersensitive response (HR) induction of Xcc and alterations in stress tolerance. Global transcriptome analyses revealed the Flp had a broad regulatory role and that most T3SS HR and pathogenicity (hrp) genes were down-regulated in the flp mutant. ß-glucuronidase activity assays implied that Flp regulates the expression of hrp genes via controlling the expression of hrpX. More assays confirmed that Flp binds to the promoter of hrpX and affected the transcription of hrpX directly. Interestingly, the constitutive expression of hrpX in the flp mutant restored the HR phenotype but not full virulence. Taken together, the findings describe the unrecognized regulatory role of Flp protein that controls hrp gene expression and pathogenesis in Xcc.

Potential of siRNA-albumin complex against cancer.

RNA interference is a highly specific as well as efficient technology for gene therapy application in molecular oncology. The present study was planned to develop an efficient and stable tumor selective delivery mechanism for siRNA gene therapy for the purpose of both diagnosis as well as therapy. We have used 20 Male wistar rats for the formation of colon cancer model and utilized albumin as carrier molecule for the delivery of siRNA against vascular endothelial growth factor receptor 2 (VEGF R2). The study results confirmed efficient delivery of siRNA at tumor site as confirmed by tagging of siRNA-albumin complex with 99mTC. Moreover, the expression of VEGF also showed decline after efficient delivery of siRNA at tumor site. The study concluded that albumin is an efficient molecule for the efficient delivery of siRNA at tumor sites.

Effects of long non-coding RNA H19 and microRNA let7a expression on thyroid cancer prognosis.

This study aims to explore the effects of long non-coding RNA H19 (lncRNA H19) and microRNA let7a (miRNA let7a) expression on the prognosis of thyroid cancer (TC). This may aid in the discovery of more effective treatment and prognosis approaches for TC. Between January 2008 and January 2011, 131 TC tissues and adjacent tissues were obtained from TC patients. An additional 122 normal thyroid tissues were also collected as normal controls from patients with benign thyroid lesions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect lncRNA H19 and miRNA let7a mRNA expression. Five-year follow-ups were conducted. A Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of lncRNA H19 and miRNA let7a in TC. The Kaplan-Meier method was applied to analyze the 5-year survival rate of TC patients. Univariate and multivariate factor analyses were employed to analyze the prognostic factors of TC. The lncRNA H19 mRNA expression was higher while the miRNA let7a mRNA expression was lower in TC tissues than, in the normal thyroid tissues and adjacent tissues. The area under the ROC curve (AUC) of lncRNA H19 and miRNA let7a were 0.801 and 0.116, with sensitivity at 72.5% and 84%, as well as specificity 75.4% and 77%, respectively. In TC patients with tumor diameters≥1.0cm, lncRNA H19 mRNA expression was elevated, but miRNA let7a mRNA expression was reduced. This was also evident in TC patients with TNM stages III+IV and those with lymph node metastasis. TC patients with a lower 5-year survival rate showed upregulated levels of lncRNA H19 expression and, downregulated levels of miRNA let7a expression. LncRNA H19 and miRNA let7a expression, tumor diameter, TNM stage and lymph node metastasis were independent prognostic factors of TC. This study demonstrated that increased lncRNA H19 and decreased miRNA let7a expression levels are associated with poor prognosis in TC patients. An inverse relationship between lncRNA H19 and miRNA let7a expression levels was exhibited.

Characterization of the GntR family regulator HpaR1 of the crucifer black rot pathogen Xanthomonas campestris pathovar campestris.

The GntR family transcription regulator HpaR1 identified from Xanthomonas campestris pv. campestris has been previously shown to positively regulate the genes responsible for hypersensitive reaction and pathogenicity and to autorepress its own expression. Here, we demonstrated that HpaR1 is a global regulator that positively regulates diverse biological processes, including xanthan polysaccharide production, extracellular enzyme activity, cell motility and tolerance to various stresses. To investigate the regulatory mechanisms of HpaR1, we began with xanthan polysaccharide production, which is governed by a cluster of gum genes. These are directed by the gumB promoter. Disruption of HpaR1 significantly reduced gumB transcription and an electrophoretic mobility shift assay demonstrated that HpaR1 interacts directly with gumB promoter. DNase I footprint analysis revealed that HpaR1 and RNA polymerase were bound to the sequences extending from -21 to +10 and -41 to +29 relative to the transcription initiation site of gumB, respectively. Furthermore, in vitro transcription assays showed that HpaR1 facilitated the binding of RNA polymerase to gumB promoter, leading to an enhancement of its transcription. These results suggest that HpaR1 regulates gumB transcription via a mechanism similar but different to what was found, until now, to only be used by some MerR family transcription activators.

Rubisco Activase Is Also a Multiple Responder to Abiotic Stresses in Rice.

Ribulose-1,5-bisphosphate carboxylase/oxygenase activase (RCA) is a nuclear gene that encodes a chloroplast protein that plays an important role in photosynthesis. Some reports have indicated that it may play a role in acclimation to different abiotic stresses. In this paper, we analyzed the stress-responsive elements in the 2.0 kb 5'-upstream regions of the RCA gene promoter and the primary, secondary and tertiary structure of the protein. We identified some cis-elements of multiple stress-related components in the RCA promoter. Amino acid and evolution analyses showed that the RCA protein had conserved regions between different species; however, the size and type varied. The secondary structures, binding sites and tertiary structures of the RCA proteins were also different. This might reflect the differences in the transcription and translation levels of the two RCA isoforms during adaptation to different abiotic stresses. Although both the transcription and translation levels of RCA isoforms in the rice leaves increased under various stresses, the large isoform was increased more significantly in the chloroplast stroma and thylakoid. It can be concluded that RCA, especially RCAL, is also a multiple responder to abiotic stresses in rice, which provides new insights into RCA functions.

[Clinical analysis and follow-up study of cardiavascular system involvement in 10 children with methylmalonic aciduria combined with hyperhomocysteinemia].

OBJECTIVE: To study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC). METHODS: The clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up. RESULTS: In the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations. CONCLUSIONS: Metabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.

Unmethylated-maspin DNA in maternal plasma is associated with severe preeclampsia.

INTRODUCTION: Cell-free fetal DNA in maternal plasma is associated with complications of pregnancy, including preeclampsia. Determination of levels is affected by fetal gender and genetic polymorphisms. Unmethylated maspin (u-maspin) is present in the placenta, and is placental-specific. The purpose of this study was to determine whether u-maspin DNA in maternal blood could serve as a marker of preeclampsia by measuring levels in different trimesters of normal pregnancies and in those complicated by preeclampsia. MATERIAL AND METHODS: This case-control study was set in a tertiary care hospital. The population consisted of 45 women with normal pregnancies (15 in the 1st trimester, 15 in the 2nd trimester, 15 in the 3rd trimester), 20 women with mild preeclampsia, 25 women with severe preeclampsia, and six women with gestational trophoblastic disease. Peripheral blood was collected and methylation-specific PCR and fluorescence quantitative PCR were performed to measure the content of u-maspin DNA in maternal blood. RESULTS: U-maspin DNA was 5.5-fold higher in women with severe preeclampsia than in those with a normal 3rd trimester pregnancy (p < 0.05). During normal pregnancy, u-maspin DNA in maternal plasma tended to increase with advancing gestational age (p = 0.06). U-maspin DNA was not detected in healthy non-pregnant women or those with gestational trophoblastic disease. CONCLUSION: U-maspin DNA in maternal blood is associated with severe preeclampsia.

Retinal nerve fiber layer thickness in a population of 12-year-old children in central China measured by iVue-100 spectral-domain optical coherence tomography: the Anyang Childhood Eye Study.

PURPOSE: To study the distribution of peripapillary retinal nerve fiber layer (RNFL) thickness in a population of 12-year-old children in central China using iVue-100 spectral-domain optical coherence tomography (SD-OCT). METHODS: Twelve-year-old students (n = 2105) from four randomly selected middle schools in Anyang, China, participated in the study. Each child underwent ocular examinations, including optical biometry, cycloplegic autorefraction, and SD-OCT (iVue-100). Glaucoma optic nerve head scan was performed to measure RNFL thickness. Only the children with a signal strength index higher than 45 were included in the analyses. Multivariate analyses were performed to examine the association of RNFL with demographic variables (e.g., sex, age, and body mass index [BMI]) and ocular variables (e.g., axial length and refractive error). RESULTS: Optical coherence tomography scans of adequate quality were available for 1955 children (92.9%). The mean (SD) RNFL thickness was 103.08 (9.01) µm, with the mean (SD) thickest RNFL in the inferior quadrant (129.34 [14.90] µm), followed by the superior (126.19 [15.24] µm), temporal (82.98 [10.57] µm), and nasal (73.82 [13.89] µm) quadrants. The RNFL was thicker with shorter axial length (ß = -1.53, P < 0.0001) and with higher hyperopia (ß = 0.90, P < 0.0001). Girls had slightly thicker average RNFL thickness than boys (P < 0.0001). The RNFL thickness had no significant correlation with age or BMI. CONCLUSIONS: This study establishes normative peripapillary RNFL values of 12-year-old Chinese children as measured by iVue-100 SD-OCT. The RNFL thickness decreased significantly with increasing axial length and higher myopia.

Polymorphisms of the DNA repair genes XPD and XRCC1 and the risk of age-related cataract development in Han Chinese.

PURPOSE: Epidemiological evidence suggests that ultraviolet (UV) irradiation and oxidative stress play an important role in age-related cataract pathogenesis. UV irradiation and oxidative stress can produce a wide range of DNA damage. Polymorphisms of DNA repair enzymes may affect repair efficiency and the role of DNA repair mechanisms has received attention recently in age-related cataract pathogenesis. In this case-control study, The aim was to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD) codon 751 and x-ray cross-complementing group 1 (XRCC1) codon 399, in patients with age-related cataract and in healthy controls. METHODS: Polymerase chain reaction and restriction fragment length polymorphisms were used to analyze XPD T751G and XRCC1 G399A in 180 patients with age-related cataract and 174 healthy individuals as controls. RESULTS: There was a significant difference between the case and control groups in the XRCC1399 genotype. The odds ratio of the XRCC1 G/A polymorphism compared with the G/G wild-type genotype was 1.92 (95% CI = 1.17-3.15, p = 0.01). Moreover, individuals who carried at least one A-allele (G/A or A/A) had a 1.68-fold increased risk of developing age-related cataract compared with those who carried the G/G wild type genotype (OR = 1.68; 95% CI: 1.05-2.68, p = 0.030). No statistically significant difference was found in the genotypic and allelic distributions of the polymorphisms in the XPD gene between the groups. CONCLUSIONS: These results suggest that polymorphisms in XRCC1 codon 399 may be associated with the development of age-related cataract in Han Chinese.

[Novel CHST6 compound heterozygous mutations cause macular corneal dystrophy in a Chinese family].

OBJECTIVE: The aim of this study was to identify mutations of CHST6 gene in a Chinese family with macular corneal dystrophy (MCD) and to investigate the histopathological changes of MCD. METHODS: Corneal button of the proband was obtained from penetrating keratoplasty for the treatment of severe corneal dystrophy. The sections and ultrathin sections of this specimen were examined under light microscope and transmission electron microscope (TEM). Genomic DNA was extracted from leukocytes in peripheral blood from the family members. The coding region of CHST6 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by direct sequencing and restriction enzyme digestion. RESULTS: Histochemical study revealed positive results of colloidal iron stain. TEM revealed enlargement of smooth endoplasmic reticulum and the presence of intracytoplasmic vacuoles. Two mutations, Q298X Y358H, were identified in exon 3 of CHST6. Three patients were compound heterozygotes of these two mutations. The C892T transversion occurred at codon 298 turned the codon of glutamine to a stop codon; the T1072C transversion occurred at codon 358 caused a missense mutation, tyrosine to histidine. All six unaffected family members were heterozygotes. These two mutations were not detected in any of the 100 control subjects. CONCLUSIONS: The novel compound heterozygous mutation results in loss of CHST6 function and causes the occurrence of MCD. This is the first report of this gene mutation.

[Analysis of TGFBI gene mutation in a Chinese family with atypical Reis-Buckler corneal dystrophy].

OBJECTIVE: To identify the TGFBI gene mutation and the relationship between genotype and phenotype of a Chinese family with atypical Reis-Buckler corneal dystrophy (RBCD). METHODS: Four patients, two non-carrier relatives of the family were enrolled in the present study. In addition to ophthalmologic examinations, PCR amplification and DNA sequencing of exons 4, 11, 12, and 14 of the TGFBI gene were carried out. Exon 14 was also sequenced in 100 healthy controls. RESULTS: A G to A transition at codon 623 in all affected members was identified. This mutation resulted in a substitution of glycine (GGC) to aspartic acid (GAC) at the protein level.None of the healthy family members, or any of the 100 control subjects carried this mutation. CONCLUSION: The G623D mutation of the TGFBI gene caused an atypical Reis-Buckler corneal dystrophy in this family. This mutation is reported in Chinese for the first time.

[TGFBI gene mutation analysis in a Chinese family with Thiel-Behnke corneal dystrophy].

OBJECTIVE: To identify the gene mutation in autosomal dominant Thiel-Behnke corneal dystrophy affecting a five-generation Chinese family. To study the TGFBI gene mutation in Chinese patients with Thiel-Behnke corneal dystrophy by molecular genetic analysis. METHODS: Ophthalmologic examinations were performed in 10 patients and two normal family members in an autosomal dominant Thiel-Behnke corneal dystrophy family. Five ml peripheral blood was collected and Genomic DNA was extracted using salt fractionation. The exons 4, 7, 8, 11 and 12 of the TGFBI gene were amplified by PCR and mutation analysis was performed by direct sequencing. RESULTS: Mutation analysis of the exons 4, 7, 8, 11 and 12 of the TGFBI gene identified a G-->A missense mutation in the exon 12 by bidirectional sequencing. This mutation resulted in a substitution of glutamine for arginine at amino acid 555 (R555Q) of the protein. This mutation existed in all of the patients, but not in unaffected individuals. CONCLUSION: Thiel-Behnke corneal dystrophy in this family is caused by R555Q mutation of the TGFBI gene, the phenotypes of this corneal dystrophy are closely correlated with TGFBI mutation.

[Mutation analysis of FOXL2 in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome].

OBJECTIVE: To identify the genetic mutation in two Chinese families and 6 sporadic patients with belpharophimosis-ptosis-epicanthus inversus syndrome (BPES). METHODS: Polymorphisms of 5 satellite markers on 3q were analyzed and linkage analysis was performed using linkage software (MLINK) in all cases of two families. FOXL2 gene fragments were amplified by PCR and mutation was determined by sequencing DNA fragments in all patients. RESULTS: The BPES locus in the pedigrees was mapped to 3q23, a 9.88 cM interval between markers D3S3696 and D3S1744. The maximum lod scores were 2.11 (theta = 0.00) at D3S1549 and D3S3586 and 1.51 (theta = 0.00) at D3S1764. By direct sequencing FOXL2 gene, two sporadic cases had a 30-bp in frame duplication 909 - 938 dup 30 and one sporadic case showed a nucleotide insertion 1041 - 1042 ins C. However, it was unable to find any causal mutation of FOXL2 in two families with BPES. CONCLUSIONS: The gene responsible for BPES in two Chinese families was linked to D3S1549, D3S3586 and D3S1764. This is the first reported mutations of FOXL2 (909 - 938 dup 30 and 1041 - 1042 ins C) in Chinese sporadic cases. One of the mutations, in-frame 30-bp duplication (909 - 938 dup 30), is one of the most common mutation hotspots in the coding region of FOXL2. In BPES families without FOXL2 mutation, it cannot be excluded that the disorder is caused by a position effect in the surrounding region of FOXL2 gene or by other genes located at 3q23.

[A research on TGFBI gene mutations in Chinese families with corneal dystrophies].

OBJECTIVE: To identify what kind of TGFBI gene mutation happening to Chinese patients with corneal dystrophies. METHODS: Three Chinese families with stromal corneal dystrophies and one Chinese family with Thiel-Behnke corneal dystrophies were studied, of whom three were Han race and another was Mongolia race in China. All members of families were examined clinically and their genomic DNAs were extracted from blood leukocytes. Thirteen exons in TGFBI gene were amplified by polymerase chain reaction (PCR) and directly sequenced for molecular analysis. RESULTS: Mutations in TGFBI gene were detected from all the patients with corneal dystrophy, but not found in normal subjects of families. The mutation R555W was found and identified from the family with granular corneal dystrophy; R555Q from the family with Thiel-Behnke corneal dystrophy; and R124H from the other two families with Avellino corneal dystrophy. CONCLUSION: The above study results show that the amino acids R124 and R555, if their genetic codes result from the mutations, play an important role in the pathogenesis of autosomal dominant corneal dystrophy of Chinese patients, and the molecular genetic analysis can improve the accuracy of diagnosing corneal dystrophy. In China, the mutation R555Q found in the family with Thiel-Behnke corneal dystrophy is reported for the first time.

[Autosomal dominant congenital golden crystal nuclear cataract caused by a missense mutation in gammaD crystallin gene (CRYGD) in a Chinese family].

OBJECTIVE: To identify genetic defects associated with autosomal dominant congenital golden crystal nuclear cataract (ADCC) in a Chinese pedigree of northern China. METHODS: Clinical data were collected and the lens changes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was obtained from blood leucocytes. Linkage analyses was conducted using polymorphisms of 21 microsatellite markers and mutational analyses of candidate genes was studied by direct sequencing. RESULTS: The maximum LOD score (1.505 at recombination fraction theta = 0.00) was obtained at markers D2S1782, D2S1384 and D2S1385 near the gamma-crystallin gene (CRYG) cluster within 2q33 - q35. Sequencing analysis of the coding regions of the CRYGA. B, C, and D genes showed that the there was a heterozygous C-->A transversion at position 109 (R36S) in exon 2 of CRYGD gene, which was co-segregated with the affected members. CONCLUSIONS: R36S mutation in CRYGD gene results in an ADCC phenotype that is different from previous reports. This finding indicates that the presence of phenotypic heterogeneity of cataract, especially in different races. This is the first report of congenital cataract caused by R36S mutation in CRYGD gene.

[Gene mapping of a pedigree with autosomal dominant congenital cataract].

OBJECTIVE: To map the gene for autosomal dominant congenital cataract (ADCC) in a Chinese family. METHODS: Blood samples were collected from 14 members of this family. Linkage analysis was carried out using short tandem repeat polymorphism (STRP) in close proximity to genes and loci previously reported involving in human cataract. Two-point linkage analysis lod scores were calculated. RESULTS: The mutation gene locus in this pedigree was mapped to 17q, an 11.78-cM interval between markers D17S1288 and D17S933. Significant positive maximum LOD scores (Z(max)) at recombination fraction (theta) 0, were obtained for markers D17S805 (Z(max) = 2.03), D17S1294 (Z(max) = 2.49), and D17S1293 (Z(max) = 2.22). CONCLUSIONS: The mutation gene in this ADCC pedigree is located at chromosome 17q. This is the first report of an autosomal dominant congenital nuclear cataracts located at this locus. This result will be helpful for further studying of the pathogenesis of cataract.

[Autosomal dominant congenital nuclear cataract caused by a deletion mutation in the beta A1-crystallin gene].

OBJECTIVE: To identify the genetic defect causing automosal dominant congenital cataracts (ADCC) with nuclear opacities in a Chinese pedigree. METHODS: Linkage analysis was carried out with the short tandem repeat polymorphisms flanking the candidate genes. Mutation analysis of the candidate gene in the critical region was performed to detect the potential mutation. RESULTS: The cataract locus in this pedigree was mapped to 17q11.1-12, an 11.78 cM interval between markers D17S933 and D17S 1288. By means of sequencing the candiate gene, betaA1-crystallin (CRYBA1), a deletion mutation DeltaG91 in exon 4 was detected. This change cosegregated with the patients in the family but was not found in 50 normal unrelated individuals. CONCLUSION: It is a deletion mutation DeltaG91 of CRYBA1 gene that causes autosomal dominant congenital nuclear cataract. This is the first report of an autosomal dominant congenital nuclear cataract caused by the mutation in this gene.