Cataract ; genetics ; Diabetic Retinopathy ; genetics ; Eye Diseases ; genetics ; therapy ; Genetic Therapy ; Glaucoma, Open-Angle ; genetics ; Humans ; Macular Degeneration ; genetics

OBJECTIVETo detect the disease-causing mutation in a pedigree affected with autosomal dominant congenital cataract.

METHODSGenomic DNA was extracted and purified from peripheral blood samples from members of the pedigree and 100 healthy controls. Coding regions of 18 candidate genes were screened with PCR and Sanger sequencing. Identified mutations were verified among 100 healthy individuals to exclude single nucleotide polymorphisms.

RESULTSA heterozygous nonsense mutation c.471G>A of the CRYGD gene, which resulted in p.Trp157Term, was identified in all three patients. The same mutation was not found in the two normal individuals from the family and 100 healthy controls. The nonsense mutation was predicted to be "disease causing" by Mutation t@sting program.

CONCLUSIONThe nonsense mutation c.471G>A of the CRYGD gene probably underlies the congenital cataract in the pedigree.

Cataract ; etiology ; genetics ; Child ; Codon, Nonsense ; Humans ; Male ; Sequence Analysis, DNA ; gamma-Crystallins ; genetics

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital cataracts. METHODS: Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes. RESULTS: By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing. CONCLUSION The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.
Asian Continental Ancestry Group ; Cataract ; congenital ; genetics ; China ; Heterozygote ; Humans ; Mutation ; Pedigree ; gamma-Crystallins ; genetics

OBJECTIVETo identify the disease-causing gene mutations in three Chinese pedigrees affected with congenital inherited cataract, in ordre to provide genetic counseling and prenatal diagnosis.

METHODSUsing exons combined target region capture sequencing chip to screen the candidate disease-causing mutations, Sanger sequencing was used to confirm the disease-causing mutations.

RESULTSFamily 1 was polymorphic cataract, family 2 was cerulean cataract, family 3 was coralliform cataract. The inheritance mode of the three pedigrees consisted with autosomal dominant inheritance. In family 1, a nonsense mutation of CRYβB2 gene c.463C>T in exon 6 result in a p.Q155X amino acid change. In family 2, a missense mutation of of CRYGD gene c.43C>T in exon 2 result in a p.R14C amino acid change. In family 3, a missense mutation of CRYGD gene c.70C>A in exon 2 result in a p.P23T amino aid change. No above-mentioned mutations were found in normal individuals.

CONCLUSIONThe nonsense mutation c.463C>T (p.Q155X) of CRYβB2 gene, the heterozygous mutations c.43C>T(p.R14C) of CRYGD gene and c.70C>A( p.P23T) of CRYGD gene was the disease-causing gene mutation in family 1, 2 and 3 respectively, our results provid genetic counseling and prenatal diagnosis for these three families.

Cataract ; genetics ; Genetic Counseling ; Humans ; Mutation ; Pedigree ; Prenatal Diagnosis ; beta-Crystallin B Chain ; genetics ; gamma-Crystallins ; genetics

Adolescent ; Adult ; Cataract ; congenital ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Young Adult

PURPOSE: The concordance of strabismus in monozygotic twins was examined in order to study the role of genetics in the different types of strabismus. METHODS: The medical charts of 39 pairs of monozygotic twins (63 of 78 subjects had strabismus) dated between May 1985 and December 2005 were reviewed retrospectively. We analyzed each case by refraction, type of strabismus, age of onset, amount of deviation, and stereopsis. RESULTS: Twenty-three of 39 pairs of twins (59%) showed phenotypic concordance; 15 of 21 pairs showed intermittent exotropia (71%), five of nine pairs showed infantile esotropia (55%), and three of four pairs showed partially accommodative esotropia (75%). All pairs with accommodative esotropia showed discordance. One discordant pair showed infantile esotropia, one expressed infantile esotropia, and another expressed sensory exotropia due to congenital cataract. CONCLUSIONS: The concordance rate of monozygotic twins was 59% in this study. Partially accommodative esotropia and intermittent exotropia had high concordance rates of strabismic phenotypes in monozygotic twins. Based on the results of this study, it is suggested that there may be a strong genetic component regarding these types of strabismus. Concordant pairs of monozygotic twins showed similarity in onset, deviation angle, postoperative result, and recurrence.
Age of Onset ; Cataract ; Depth Perception ; Esotropia ; Exotropia ; Genetics ; Humans ; Phenotype ; Recurrence ; Retrospective Studies ; Strabismus* ; Twins, Monozygotic*

PURPOSE: The concordance of strabismus in monozygotic twins was examined in order to study the role of genetics in the different types of strabismus. METHODS: The medical charts of 39 pairs of monozygotic twins (63 of 78 subjects had strabismus) dated between May 1985 and December 2005 were reviewed retrospectively. We analyzed each case by refraction, type of strabismus, age of onset, amount of deviation, and stereopsis. RESULTS: Twenty-three of 39 pairs of twins (59%) showed phenotypic concordance; 15 of 21 pairs showed intermittent exotropia (71%), five of nine pairs showed infantile esotropia (55%), and three of four pairs showed partially accommodative esotropia (75%). All pairs with accommodative esotropia showed discordance. One discordant pair showed infantile esotropia, one expressed infantile esotropia, and another expressed sensory exotropia due to congenital cataract. CONCLUSIONS: The concordance rate of monozygotic twins was 59% in this study. Partially accommodative esotropia and intermittent exotropia had high concordance rates of strabismic phenotypes in monozygotic twins. Based on the results of this study, it is suggested that there may be a strong genetic component regarding these types of strabismus. Concordant pairs of monozygotic twins showed similarity in onset, deviation angle, postoperative result, and recurrence.
Age of Onset ; Cataract ; Depth Perception ; Esotropia ; Exotropia ; Genetics ; Humans ; Phenotype ; Recurrence ; Retrospective Studies ; Strabismus* ; Twins, Monozygotic*

Congenital cataract is a highly heterogeneous disorder at both the genetic and the clinical-phenotypic levels. A unique cataract was observed in a 4-generation Chinese family, which was characterized by autosomal dominant inheritance and late-onset. Mutations in the 13 known genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYGC, CRYBA1/A3, CRYGD, Connexin50, Connexin46, intrinsic membrane protein LIM2, cytoskeletal protein BFSP2, the major intrinsic protein-MIP and the heat shock factor HSF4) have previously been demonstrated to be the frequent reason for isolated congenital cataracts, but the exact molecular basis and underlying mechanisms of congenital cataract still remain unclear. This study was designed to find whether these 13 genes developed any mutation in the family members and to identify the disease-causing gene. Polymerase chain reaction (PCR) and direct DNA sequence analysis were carried out to detect the 13 genes. The results showed that no mutation causing amino acid alternations was found in these potential candidate genes among all patients in the family, and only several single-nucleotide polymorphisms (SNPs) were identified. A transitional mutation in the fourth intron of CRYBB2 and some silent mutations in the first exon of BFSP2 and CRYGD were found in the cataract family, but further study showed that these mutations could also be found in normal controls. It was concluded that some unidentified genes may underlie the occurrence of late-onset cataract in this family. A genome-wide screening will be carried out in the next study.
Adult ; Cataract ; congenital ; genetics ; China ; DNA Mutational Analysis ; Female ; Genes, Dominant ; Humans ; Male ; Middle Aged ; Pedigree

OBJECTIVE: To explore the genetic basis for a pedigree affected with Nance-Horan syndrome. METHODS: Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity. RESULTS: A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4). CONCLUSION The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.
Cataract/genetics* ; Genetic Diseases, X-Linked ; Humans ; Mutation ; Pedigree ; State Medicine ; Tooth Abnormalities

OBJECTIVETo map the disease locus for a congenital cataract family, and detect the disease-causing gene.

METHODSAn autosomal dominant congenital cataract family was genotyped by genome wide scan using 382 autosomal microsatellite markers from ABI-MD10. Two-point linkage analysis was carried out by the MLINK program.

RESULTSThe disease locus of this family was mapped at 12p11.2-q15. Sequence analysis of a candidate gene-major intrinsic protein (MIP) revealed a novel missense mutation G-->A at the nucleotide 702 in exon 4, which resulted in a substitution of arginine to lysine at codon 233 (p.R233K).

CONCLUSIONThe mutation G-->A at nt702 in MIP gene was associated with the binocular polymorphic congenital cataract in the family. This transition occurring at the C-terminus of MIP might decrease the stability of the C-end of the protein and impact the function of the protein.

Aquaporins ; genetics ; Base Sequence ; Cataract ; genetics ; Exons ; genetics ; Eye Proteins ; genetics ; Female ; Genome, Human ; genetics ; Genomics ; Genotype ; Humans ; Male ; Mutation, Missense ; Pedigree ; Polymorphism, Genetic ; Sequence Analysis, DNA