Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes

Purpose: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. Methods: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. Results: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III: 1; III: 2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II: 1, III: 1; III: 2) and in unaffected I: 1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. Conclusions: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA

Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes

Purpose: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. Methods: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. Results: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III:1; III: 2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2) and in unaffected I:1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. Conclusions: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA. © 2011 Molecular Vision.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Degradation of pesticides, dye molecules and relevant surface interactions with mesoporous titania

Titania is the most widely studied and applied material for photocatalytic applications. Enhancing the surface area of a titania catalyst could significantly increase its activity as photocatalytic reactions typically proceed on or near the surface of the material. In this report, mesoporous titania is used in water purification applications. The photocatalytic activity of different mesoporous TiO2 samples obtained from various synthesis approaches is tested by following the degradation of methylene blue and some highly mobile pesticides present in surface waters under UV illumination. Not only the specific surface area of the samples determines their efficiency, also the crystallinity and chemical nature of their surface are crucial. Therefore, we use Rietveld analysis to determine the crystallinity of the samples. IR spectroscopy reveals that titanol groups present on the surface play an important role in the activity of the material. This means that to further enhance the activity of the material, a lot of attention needs to be paid to the surface of TiO2 and the interactions of the organic pollutants and the surface of mesoporous titania. In the case of the degradation of the pesticides, the intermediate species are determined to make sure no toxic species are obtained

Uncommon Leber Plus Disease Associated With Mitochondrial Mutation m.11778G>A in a Premature Child.

Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed in our manuscript.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe

Uncommon Leber "plus" disease associated with mitochondrial m.11778G>A mutation in a premature child

Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed

Prevalence of AIPL1 mutations in inherited retinal degenerative disease

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA, We recently identified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interacting protein-like 1) and identified three mutations that were the cause of blindness in five families with LCA, In this study, AIPL1 was screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 LCA families whose retinal disorder is caused by homozygous or compound heterozygous AIPL1 mutations. We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy, (C) 2000 Academic Press

TMEM126A, Encoding a Mitochondrial Protein, Is Mutated in Autosomal-Recessive Nonsyndromic Optic Atrophy

Nonsyndromic autosomal-recessive optic neuropathies are rare conditions of unknown genetic and molecular origin. Using an approach of whole-genome homozygosity mapping and positional cloning, we have identified the first gene, to our knowledge, responsible for this condition, TMEM126A, in a large multiplex inbred Algerian family and subsequently in three other families originating from the Maghreb. TMEM126A is conserved in higher eukaryotes and encodes a transmembrane mitochondrial protein of unknown function, supporting the view that mitochondrial dysfunction may be a hallmark of inherited optic neuropathies including isolated autosomal-recessive forms