Disease relevance of Coloboma

• We conclude that cardiovascular malformations, coloboma, and facial asymmetry are common findings in CHARGE syndrome caused by CHD7 mutation [1].
• In this paper we have investigated the prevalence of PAX2 mutations in patients with ocular colobomas, microphthalmos, or retinal anomalies, either in isolation or with associated urogenital anomalies [2].
• The eye defects consisted of high grade myopia, microspherophakia, lens coloboma, lens luxation, and retinal detachment [3].
• Unknown syndrome: Hirschsprung's disease, microcephaly, and iris coloboma: a new syndrome of defective neuronal migration [4].
• In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX [5].

Psychiatry related information on Coloboma

• In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice [6].
• A regularly recurring pattern of associated features involving mental retardation, postnatal growth deficiency, hypogenitalism (males), small ears, cardiac defects, micrognathia, postnatal microcephaly, and ocular coloboma was identified [7].
• JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys [8].

High impact information on Coloboma

• Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux [9].
• Domain disruption and mutation of the bZIP transcription factor, MAF, associated with cataract, ocular anterior segment dysgenesis and coloboma [10].
• We mapped the Jag1 gene to mouse chromosome 2, in the vicinity of the Coloboma ( Cm ) deletion [11].
• Vax2 homozygous mutant mice display incomplete closure of the optic fissure that leads to eye coloboma [12].
• Furthermore, Pax2 mutants show extension of the pigmented retina into the optic stalks and failure of the optic fissure to close resulting in coloboma [13].

Chemical compound and disease context of Coloboma

• Other models include additional genetic variants (dopamine transporter gene knock-out mouse, coloboma mouse, Naples hyperexcitable rat, acallosal mouse, hyposexual rat, and population-extreme rodents), neonatal lesioning of dopamine neurons with 6-hydroxydopamine, and exposure to other neurotoxins or hippocampal irradiation [14].
• Despite the ubiquitous role of SNAP-25 in synaptic transmission, and uniformly decreased expression in the mutants, coloboma mice show marked deficits in Ca2+-dependent dopamine release selectively in dorsal but not ventral striatum [15].
• A rhesus monkey with a congenital coloboma of the optic nerve head associated with serous macular detachment underwent intravenous (IV), intrathecal, and retrobulbar fluorescein angiography [16].
• Previous research has determined that there is an increase in the concentration of norepinephrine but a decrease in dopamine utilization in the striatum and nucleus accumbens of coloboma mice [17].
• The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD [18].

Biological context of Coloboma

• The coloboma mutation (Cm) is a neutron-irradiation induced gene deletion located on the distal portion of mouse chromosome 2 [19].
• CHARGE association is the nonrandom association of congenital anomalies, including choanal atresia, coloboma, heart defects, retardation of growth and development, genital hypoplasia and ear abnormalities [20].
• Congenital hypodontia of maxillary lateral incisors in association with coloboma of the iris and hypomaturation type of amelogenesis imperfecta in a large kindred [21].
• We report on a 16-month-old male patient with ring chromosome 4 and deletion of Wolf-Hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices [22].

Anatomical context of Coloboma

• Hamartomatous adenoma of the nonpigmented ciliary epithelium arising in iris-ciliary body coloboma. Light and electron microscopic observations [23].
• Brain malformations consisted of lissencephaly and the Dandy-Walker anomaly; congenital cataracts, retinal dysgenesis and coloboma of the choroid were found in the eyes [24].
• In contrast to the differences between coloboma and wild-type mice, there was no significant difference in the duration or amplitude of theta rhythmic activity (4-6 Hz) induced by tail-pinch (10 s), afferent-evoked field potentials, or paired-pulse responses recorded in the dentate gyrus of SNAP-25 transgenic coloboma and wild-type mice [25].
• We describe a patient with bilateral extreme microphthalmia with bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis [26].
• We report on a patient with CHARGE syndrome, as manifested by a coloboma of the optic nerve head, congenital heart defect (ASD, VSD, and parachute mitral valve), choanal atresia, severe growth retardation, genital hypoplasia, abnormal ears, cleft lip and palate, and pectus carinatum [27].

Gene context of Coloboma

• A previous study found an association between ADHD and two polymorphisms in the 3' untranslated region (UTR) of SNAP-25, a gene encoding a synaptic vesicle docking protein known to play a role in the hyperactivity observed in the Coloboma mouse strain [28].
• PURPOSE: To investigate whether 173 patients with microphthalmia, anophthalmia, and coloboma have mutations in the eye-development gene SIX6 [29].
• The localization of the genetic abnormality in coloboma mice using the Snap gene marker will provide a powerful tool for studying the biologic basis of locomotor hyperactivity [30].
• Deletion map of the coloboma (Cm) locus on mouse chromosome 2 [31].
• It has been previously shown that mutations in a particular nucleotide in CHX10 are associated with an autosomal recessive syndrome of microphthalmia/anophthalmia with iris colobomas and cataracts in two families [32].

Analytical, diagnostic and therapeutic context of Coloboma

• Rodent animal models of ADHD, like the Spontaneously Hypertensive Rat (SHR) and other rat models such as those with chemical and radiation-induced brain lesions and cerebellar stunting, and the Coloboma mouse model exhibit clear similarities with several aspects of the human disorder and should prove useful in studying specific traits [33].
• Both static perimetry and fluorescein angiography of the midperiphery corresponding to the meridian of laser coloboma done six months after surgery showed focal damage [34].
• Other characteristic features are microcephaly, intellectual handicap, Greek helmet facies and closure deficits such as cleft lip or cleft palate, coloboma of the eye, and cardiac septal defect [35].
• Partial coloboma, observed only with transillumination techniques, occur in 16% of male patients diagnosed with Kallmann syndrome [36].
• CONCLUSIONS: Retinal detachment secondary to choroidal coloboma can be treated successfully by scleral buckling or PPV with internal tamponade [37].

References