Disease relevance of CRYGD

• Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts [1].
• In one case, reported in detail, unilateral pulmonary edema developed during administration of 0.5N saline for the treatment of diabetic acidosis via the misplaced catheter, and it reverted following repositioning of the catheter in the superior vena caca [2].
• Usefulness of a CACA repeat polymorphism in genotype assignments in Duchenne/Becker muscular dystrophy [3].

High impact information on CRYGD

• Both the polyoma enhancer fragment and the spontaneously created enhancers lack the alternating purines-pyrimidines or "CACA box" suggested to be characteristic for enhancer elements and show only limited homology to the "GTGG(AAATTT)G box."[4]
• For some years, evidence has accumulated that there are GABA receptors, especially prominent along visual pathways, which are neither antagonized by bicuculline nor activated by baclofen, but are activated by certain conformationally restricted analogues of GABA, including cis-4-aminocrotonic acid (CACA) [5].
• To our knowledge, these findings are the first evidence of an involvement of CRYGC and support the role of CRYGD in human cataract formation [6].
• It involves the third known mutation in the CRYGD gene but offers, for the first time, a causative explanation of the phenotype [7].
• Sequencing of the CRYGD gene has shown a heterozygous C-->A transversion in position 109 of the inferred cDNA (36R-->S transversion of the processed, N-terminal methionine-lacking CRYGD) [7].

Biological context of CRYGD

• A new congenital nuclear cataract caused by a missense mutation in the gammaD-crystallin gene (CRYGD) in a Chinese family [8].
• CONCLUSIONS: The R36S mutation in CRYGD identified in this Chinese family caused a nuclear golden crystal cataract phenotype not described before [8].
• Haplotyping indicated that the disease gene lay in the approximate 10 Mb physical interval between D2S1384 and D2S128, containing the gamma-crystallin gene (CRYGA-CRYGD) cluster on chromosome 2q33.3-q34 [9].
• Interventions included complete ophthalmological examination, cataract phenotype characterization, PCR amplification, and automated DNA sequencing of the 2 exons and exon/intron junctions of the CRYGD gene [10].
• Mutation analysis of the gamma-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of gammaD-crystallin (CRYGD) [11].

Anatomical context of CRYGD

• Tritiated CACA binds to cerebellar membranes in a GABA-sensitive, baclofen-insensitive manner [12].

Associations of CRYGD with chemical compounds

• Crystal analysis with subsequent automatic Edman degradation and matrix-associated laser desorption ionization time-of-flight mass spectrometry have identified the crystal-forming protein as gammaD-crystallin (CRYGD) lacking the N-terminal methionine [7].
• Sequencing of the gammaD-crystallin gene (CRYGD) revealed a C>T transition in exon 2, that causes a conservative substitution of Arg to Cys at codon 14 (R14C) [13].
• The relative effectiveness of GABA, muscimol, trans- and cis-4-aminocrotonic acid (TACA and CACA) was determined at this GABAC receptor site after cells were bathed in choline Ringer to eliminate the transporter current and in the presence of 100 microM bicuculline methiodide to block GABAA receptor current.(ABSTRACT TRUNCATED AT 400 WORDS)[14]
• gamma-Aminobutyric acid (GABA), trans-4-aminocrotonic acid (TACA), muscimol, imidazole-4-acetic acid (I4AA), cis-4-aminocrotonic acid (CACA), and isoguvacine are all GABA(C) receptor agonists [15].
• Agonist potency for the receptor is TACA > muscimol > GABA > I-4AA > isoguvacine > 3-APS > CACA > THIP [16].
• These data suggest that the cataractogenic effect of serine at site 23 in the N-terminal domain of CRYGD may be compensated indirectly by amino acid changes in a distal domain [17].

Other interactions of CRYGD

• Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous C>A transversion in exon 2 of CRYGD that is associated with cataracts in this family [1].
• Eleven C. capucinus chromosomes are homologous to 11 human chromosomes: CCA 2 = HSA 4; CCA 3 = HSA 6; CCA 12 = HSA 9; CCA 16 = HSA 11; CCA 10 = HSA 12; CCA 11 = HSA 13; CCA 20 = HSA 17; CCA 8 = HSA 19; CCA 23 = HSA 20; CCA 24 = HSA 22; and CCA X = HSA X [18].

Analytical, diagnostic and therapeutic context of CRYGD

• RESULTS: Sequence analysis of CRYGC and CRYGD genes excluded possible causative mutations but identified known polymorphisms [19].

References