Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35

Rogaev, Evgeny I.; Rogaeva, Ekaterina; Коровайцева, Г. И.; Farrer, Lindsay A.; Petrin, A. N.; Keryanov, Sergey A.; Turaeva, Shirine; Chumakov, Ilya; George-Hyslop, Peter St; Ek, Ginter

doi:10.1093/hmg/5.5.699

Cited by 47 publications

(28 citation statements)

References 27 publications

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“…In addition, while the pathophysiology of congenital and hereditary cataracts differs in fundamental ways from that of age related cataracts, the study of congenital cataracts can provide insights into the mechanisms of lens transparency and to some of the ways in which it can be lost as the lens ages. 2q33-q35 [103], [104], [105], [106] 123660, 123680, 601286 …”

Section: Other Proteinsmentioning

confidence: 99%

Congenital cataracts and their molecular genetics

Hejtmancik¹

2008

Seminars in Cell & Developmental Biology

284

248

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Cataract can be defined as any opacity of the crystalline lens. Congenital cataract is particularly serious because it has the potential for inhibiting visual development, resulting in permanent blindness. Inherited cataracts represent a major contribution to congenital cataracts, especially in developed countries. While cataract represents a common end stage of mutations in a potentially large number of genes acting through varied mechanisms in practice most inherited cataracts have been associated with a subgroup of genes encoding proteins of particular importance for the maintenance of lens transparency and homeostasis. The increasing availability of more detailed information about these proteins and their functions and is making it possible to understand the pathophysiology of cataracts and the biology of the lens in general. Transparency and the LensThe lens transmits light with wavelengths from 390 nm to 1200 nm efficiently, extending well above the limit of visual perception (about 720 nm). Lens transparency results from appropriate architecture of lens cells and tight packing of their proteins, resulting in a constant refractive index over distances approximating the wavelength of light [1], [2]. Ultrastructurally, the lens comprises an anterior layer of organelle rich cuboidal epithelial cells covering a large fiber cell mass making up the bulk of the lens (Fig. 1). Layers of nucleated cortical fiber cells form highly ordered concentric shells around the nonnucleated and essentially organelle-free central fiber cells which make up the lens nucleus. The ends of the more peripheral fiber cells abut in branched anterior and posterior sutures. The cellular architecture and arrangement of the fiber cells and particularly their sutures are critical for light transmission and lens transparency [3]. In addition, the stability and close ordering of lens crystallins, which make up 80−90% of the soluble proteins in the lens, are critical for lens transparency. The high protein content of the lens and especially the lens nucleus, approximately 60% of the wet weight --the highest of any tissue, is particularly important for refraction and focusing of light. Solutions of lens crystallins are highly transparent, and as they are concentrated to levels above 450 mg/ml, light scattering actually decreases [4], [5].Cataracts, which can be defined as lens opacities, have multiple causes, but are often associated with breakdown of the lens microarchitecture [3], [6], possibly including vacuole formation and disarray of lens cells, which can cause large fluctuations in density resulting in light scattering. In addition, light scattering and opacity will occur if there is a significant amount of high molecular weight protein aggregates of approximately 1000 Å or more in size [7], [8]. The short-range ordered packing of the lens crystallins is important in this regard. For transparency, crystallins must exist in a homogeneous phase with significant short-range spatial Publisher's Disclaimer: This is a PDF file of an un...

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Section: Other Proteinsmentioning

confidence: 99%

Congenital cataracts and their molecular genetics

Hejtmancik¹

2008

Seminars in Cell & Developmental Biology

284

248

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“…In this study, we report the cloning, characterization and mapping of a new ABCA subfamily gene. This gene, ABCA12, is located on chromosome 2q34, in a region harboring gene(s) for lamellar ichthyosis type 2 (Parmentier et al, 1996), polymorphic congenital cataract (Rogaev et al, 1996), and insulin-dependent diabetes mellitus (IDDM13) (Morahan et al, 1996).…”

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confidence: 99%

Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34

Annilo

Shulenin

Chen

et al. 2002

Cytogenet Genome Res

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The ABCA subfamily of ABC transporters includes ten members to date. In this study, we describe an additional gene, ABCA12. Four full-length cDNA sequences have been obtained from human placenta that contain two different polyadenylation sites and two splicing forms, coding for ABCA12 isoforms of 2,595 and 2,516 amino acid residues. Both isoforms are predicted to have two ATP-binding domains (nucleotide binding domain, NBD) and two transmembrane (TM) domains, features shared by all other ABCA subfamily proteins. ABCA12 is most closely related to ABCA1, with an amino acid similarity of 47%. Northern blot analysis demonstrates that a 9.5-kb transcript is mainly expressed in the stom- ach. ABCA12 was mapped to human chromosome 2q34. Two other genes from ABCA subfamily are associated with human inherited diseases, ABCA1 with the cholesterol transport disorders Tangier disease and familial hypoalphalipoproteinemia, and ABCA4 with several retinal degeneration disorders. The ABCA12 gene is located in a region of chromosome 2q34 that harbors the genes for lamellar ichthyosis, polymorphic congenital cataract, and insulin-dependent diabetes mellitus (IDDM13), and therefore is a positional candidate for these pathologies.

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“…9 Another large Moroccan pedigree with cerulean (blue dot) cataract (CCA3, MIM 608983) mapped to a region of chromosome 2q33-q35, and a missense mutation (P23T) in the CRYGD gene as the causative mutation. 10 The same mutation has also been found in different Saudi families with cerulean cataract. 11 A fourth cerulean locus in an Indian family has been mapped to 16q23.1, with a missense mutation in MAF gene; 12 some affected members of this family also had microcornea.…”

Section: Introductionmentioning

confidence: 61%

A novel locus for autosomal dominant congenital cerulean cataract maps to chromosome 12q

et al. 2011

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Cataracts are the commonest cause of blindness worldwide. Inherited cataract is a clinically and genetically heterogeneous disease that most often shows autosomal dominant inheritance. In this study, we report the identification of a novel locus for cerulean cataract type 5 (CCA5), also known as blue-dot cataract on chromosome 12q24. To date, four loci for autosomal dominant congenital cerulean cataract have been mapped on chromosomes, 17q24, 22q11.2-12.2, 2q33-35 and 16q23.1. To map this locus we performed genetic linkage analysis using microsatellite markers in a five-generation English family. After the exclusion of all known loci and several candidate genes we obtained significantly positive LOD score (Z) for marker D12S1611 (Z max ¼3.60; at h¼0). Haplotype data indicated that CCA5 locus lies within a region of 14.3 Mb interval between the markers D12S1718 and D12S1723. Our data are strongly suggestive of a new locus for CCA5 on chromosome 12.

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Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35

Cited by 47 publications

References 27 publications

Congenital cataracts and their molecular genetics

Congenital cataracts and their molecular genetics

Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34

A novel locus for autosomal dominant congenital cerulean cataract maps to chromosome 12q

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