Autosomal Dominant Cataract Research Articles

Anterior polar cataract: clinical spectrum and genetic linkage in a single family.

Anterior polar cataract can occur as a sporadic finding, in association with other ocular abnormalities or as an inherited, autosomal dominant disorder. We have demonstrated linkage in a family with autosomal dominant anterior polar cataract to the short arm of chromosome 17, locating the gene to the region 17p12-13. All affected members of this large family had an opacity at the anterior pole of the lens that varied only in size and the effect on visual acuity. Anterior polar cataract is thought to have a minimal effect on visual acuity although in the affected members of this family there was a high incidence of unilateral amblyopia.

5-33-06 Proximal myotonic dystrophy — a family with autosomal dominant muscular dystrophy, cataracts, hearing loss, male hypogonadism and insulin resistance

5-33-06 Proximal myotonic dystrophy — a family with autosomal dominant muscular dystrophy, cataracts, hearing loss, male hypogonadism and insulin resistance

Proximal myotonic dystrophy—a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes?

We describe a family with an autosomal dominant, multisystem disorder, consisting of late-onset proximal muscular dystrophy, electrophysiological myotonia, cataracts, late-onset deafness and male hypogonadism. Four patients were available for clinical examinations. Examination of asymptomatic family members revealed another patient with bilateral cataracts but without definite muscle disorder. Five deceased members of the family had proximal muscle weakness, reportedly or confirmed in medical records. Molecular examination of genomic DNA showed no expansion of the unstable (CTG)n trinucleotide repeat on chromosome 19q13.3 associated with myotonic dystrophy (DM). Linkage to two loci implicated in other myotonic disorders, the muscle chloride channel ( CLCN1) gene, and the muscle sodium channel ( SCN4A) gene, was assessed and excluded. The clinical findings differ from those described in proximal myotonic myopathy (PROMM), in terms of the more severe muscle involvement with atrophy of affected muscles and the hearing loss. These findings suggest phenotypic and probably genetic heterogeneity among the proximal myotonic syndromes.

A New Locus for Dominant “Zonular Pulverulent” Cataract, on Chromosome 13

Inherited cataract is a clinically and genetically heterogeneous disease that most often presents as a congenital autosomal dominant trait. Here we report the linkage of a new locus for dominant "zonular pulverulent" cataract (CZP) to chromosome 13. To map the CZP locus we performed molecular-genetic linkage analysis using microsatellite markers in a five-generation English pedigree. After exclusion of eight known loci and several candidate genes for autosomal dominant cataract, we obtained significantly positive LOD scores (Z) for markers D13S175 (maximum Z [Zmax] = 4.06; maximum recombination frequency [theta max] = 0) and D13S1236 (Zmax = 5.75, theta max = 0). Multipoint analysis gave Zmax = 6.62 (theta max = 0) at marker D13S175. Haplotype data indicated that CZP probably lies in the centromeric region of chromosome 13, provocatively close to the gene for lens connexin46.

A locus for autosomal dominant posterior polar cataract on chromosome 1p.

Autosomal dominant congenital cataract is a clinically and genetically heterogeneous lens disease. Here we report the linkage of a locus for autosomal dominant posterior polar cataract (CPP) to the distal short arm of chromosome 1. To map the CPP locus we performed molecular genetic linkage analysis using microsatellite markers in a three-generation pedigree. After exclusion of 13 known loci and candidate lens genes for autosomal dominant cataract, we obtained significantly positive LOD scores for markers D1S508 (Z = 3.14, theta = 0) and D1S468 (Z = 2.71, theta = 0). Multipoint analysis gave a maximum LOD score of 3.48 (theta = 0.07) between markers D1S508 and D1S468. From haplotype data, however, CPP probably lies in the telomeric interval D1S2845-1pter, which includes the locus for the clinically distinct Volkman congenital cataract (CCV). This study provides the first evidence for genetic heterogeneity of autosomal dominant posterior polar cataract for which a locus had been linked previously to chromosome 16q.

A locus for autosomal dominant anterior polar cataract on chromosome 17p.

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.

The clinical and genetic heterogeneity of autosomal dominant cataract.

ABSTRACT As part of a linkage study we have reviewed over 150 patients with autosomal dominant cataract and suggest a clinical classification of the different phenotypes consisting of anterior and posterior polar, nuclear, cortical, blue‐dot, lamellar, coralliform and pulverulent cataracts.

Autosomal Dominant Zonular Cataract With Sutural Opacities in a Four-Generation Family

We identified and examined four generations of a family with coexisting autosomal dominant zonular cataracts and sutural opacities and sought to determine their genetic basis. Twenty-four of the 48 members in the family were examined. Systemic and ocular histories were obtained, and a detailed ophthalmic examination was performed. From each individual, 20 ml of blood was drawn for linkage studies with microsatellite markers in regions to which zonular cataracts had previously been localized (chromosomes 1, 2, and 16). Individuals of the first generation were reportedly asymptomatic. Several members of the second generation had morphologically identical zonular cataracts. Affected members of the third generation showed morphologic heterogeneity, with the zonular opacity varying from a uniform lamella to a segregation of dots. A high degree of consanguinity in the second generation suggested recessive inheritance with a pseudodominant inheritance pattern. However, examination of one member of the asymptomatic first generation disclosed senile cataractous changes superimposed on a faint zonular cataract enclosing sutural opacities and a pulverulent fetal nucleus. The latter findings were reconfirmed to be present in affected members of all generations, suggesting an autosomal dominant mode of inheritance. Initial efforts at linkage analysis excluded the gene locus causing this cataract from the Duffy, haptoglobin, and gamma-crystallin regions. The cataract in this family is both phenotypically and genetically distinct from previously described and mapped cataracts.

Mutations in the founder of the MIP gene family underlie cataract development in the mouse.

The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication. Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an autosomal recessive form of nephrogenic diabetes insipidus and absence of the Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene underlies 'big brain' development in Drosophila. Here we show that distinct mutations in the murine Mip gene underlie one form of autosomal dominant cataract in the mouse. The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP. The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane. These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens.

Mapping of Six Dominant Cataract Genes in the Mouse

The mapping of six mouse autosomal dominant cataract mutations that were induced by mutagenic treatment with radiation or ethylnitrosourea is described. Three, with differing phenotypes, mapped on Chromosome 1 between the loci of fuzzy ( fz) and leaden ( ln) and close to the locus of the γ-crystallin gene cluster. One of these, Cat-2 t, had previously been shown to be a member of a group of five allelic mutants. In addition, the previously known mutant eye lens obsolescence, Elo, maps to the same point. There are thus now eight mutants that map to this point and that may involve mutations in one of the γ-crystallin genes. In addition, one of these mutants may be a homologue of Coppock cataract in man, which also maps close to the γ-crystallin locus. Of the three remaining mutants, one, with the suggested symbol Cat-5, mapped to the proximal region of Chromosome 10, 23.4 ± 4.0 cM from downless ( dl), a region with homology to human 6q. A second mutant, provisionally designated Opj, mapped on Chromosome 16, 8.2 ± 3.9 cM from the marker mahoganoid ( md). Thus, it possibly has a homologue on human 22q, a region in which one of the β-crystallin loci is sited. A third mutant, provisionally designated Npp, mapped to Chromosome 5, 1.3 ± 0.9 cM from the locus of W, and thus probably has a homologue on human Chromosome 4.

Cataracts, aberrant oral frenula, and growth retardation: A new autosomal dominant syndrome

We report on a mother and her two children with an autosomal dominant cataract syndrome with associated aberrant oral frenula, growth retardation, and specific facial appearance. Their phenotype differs from that of other reported cataract syndromes, and we conclude that this is a previously undescribed entity.

The transcripts of zeta-crystallin, a lens protein related to the alcohol dehydrogenase family, are altered in a guinea-pig hereditary cataract

Zeta-Crystallin, a major component of the guinea-pig lens proteins, is distantly related to the enzymes of the zinc-containing alcohol dehydrogenase family (ADH). Analysis of the structural similarities between ζ-crystallin and ADH reveals that while characteristics important in maintaining the tertiary structure of the molecule appear conserved, the amino acids binding the catalytic zinc atom are absent in ζ-crystallin. Significantly, ζ-crystallin does not have ADH activity. Previous studies showed that the ζ-crystallin protein is modified in the lens of guinea-pigs affected with an autosomal dominant hereditary cataract. We have further investigated the molecular origin of the lens defect by examining the steady-state levels of ζ-crystallin transcripts in normal and mutant eyes. Our data indicate that no normal ζ-crystallin mRNA is present in the lens of the homozygous animals; instead, a cross-hybridizing lower molecular weight mRNA is detected at significantly reduced concentrations. Heterozygous lenses exhibit both mRNA species.

Phenotypic characterization and genetic analysis of twenty dominant cataract mutations detected in offspring of irradiated male mice.

SummaryTwenty autosomal dominant cataract mutations were detected among the offspring of male mice irradiated with γ- or X-rays. The single or fractionated doses ranged from 5.34 to 10.2 Gy. The phenotypic manifestation and penetrance of the mutations as well as fertility and viability of the mutants were studied by extensive breeding. Manifestation of 4 mutations was limited to the lens. Sixteen mutations were characterized by multiple ocular anomalies, of which 4 mutations also affected other organs of the body. Seventy per cent of the mutations caused severe opacity of the lens or lens and cornea. Homologous hereditary diseases in man would be juvenile cataracts with serious impairment of vision or blindness. Expressivity of the lens opacities was almost constant whereas the accompanied defects varied with respect to their severity in different individuals as well as in eyes of an individual. Phenotypic differences dependent on the genetic background could not be observed. Fourteen mutations were classified as mutations with complete penetrance without any effect on viability and fertility of heterozygotes. Four other mutations were shown to be fully penetrant but the viability of the heterozygotes was impaired. Two mutations had incomplete penetrance with no viability or fertility effects. Of the 14 mutations with complete penetrance and normal viability and fertility 6 were shown to be homozygous viable, 1 semi-lethal and 7 lethal.

Autosomal dominant cataract and microcornea associated with myopia in a Sicilian family.

A Sicilian family is reported in which 36 individuals, in 5 successive generations, were affected with congenital cataracts, microcornea and myopia with an autosomal pattern of inheritance.

Autosomal dominant anterior polar cataracts associated with a familial 2;14 translocation.

We describe a family in which autosomal dominant anterior polar cataracts are segregating in four members over three generations with an apparently balanced reciprocal translocation between chromosomes 2 and 14....