Ocular Manifestations in the Inherited DNA Repair Disorders

Dollfus, Hélène; Porto, Fernanda Belga Ottoni; Caussade, P.; Speeg-Schatz, C.; Sahel, José‐Alain; Grosshans, É; Flament, J; Sarasin, Alain

doi:10.1016/s0039-6257(02)00400-9

Cited by 84 publications

(49 citation statements)

References 123 publications

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“…The first is infantile Cockayne syndrome subtype II, which is symptomatic at birth and associated with serious eye abnormalities. 4 The second is the clinically distinct cerebro-oculofacial-skeletal syndrome, 39,40 which shares many features with severe subtype II Cockayne syndrome. The third is a disorder in one kindred 41 resembling the severe DeSanctis-Cacchione variant of xeroderma pigmentosum neurologic disease.…”

Section: Geneticsmentioning

confidence: 99%

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Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

et al. 2006

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Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31½ years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.

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Section: Geneticsmentioning

confidence: 99%

“…Cataracts, pigmentary retinopathy, and optic atrophy contribute to visual loss. 4 Neuropathology shows a small cerebrum and cerebellum with enlarged ventricles, cerebral atherosclerosis and microvasculopathy, basal ganglia and cerebellar calcification, so-called "tigroid" leukoencephalopathy, cerebellar atrophy, and a demyelinating peripheral neuropathy.…”

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confidence: 99%

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

et al. 2006

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“…The disruption of ERCC6 is causal to a subtype of Cockayne syndrome, an autosomal, recessive human disorder marked by striking somatic and neurological impairment (31). Clinical symptoms of Cockayne syndrome include hypersensitivity to sunlight, severe postnatal growth failure of the soma and brain, and progressive multiorgan and retinal degeneration (32)(33)(34).…”

mentioning

confidence: 99%

Synergic effect of polymorphisms inERCC65′ flanking region andcomplement factor Hon age-related macular degeneration predisposition

Tuo

Ning²,

Bojanowski³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional singlenucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C؊6530>G SNP in the 5 flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C؊6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C؊6530>G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C؊6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex.Cockayne syndrome ͉ single nucleotide polymorphism ͉ gene regulation ͉ interaction ͉ DNA repair A ge-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in Western countries among the elderly (1). AMD is a significant health problem in the United States, with a current estimate of Ϸ1.75 million persons with advanced AMD in the general population and Ϸ7.3 million people with early stages of AMD defined by large retinal drusen. By the year 2020, it is estimated that Ϸ2.95 million people will suffer advanced AMD, and an additional 6.4 million white individuals will have the early stages of AMD in at least one eye (2).The etiology of AMD remains elusive. To date, age and cigarette smoking have been identified as AMD risk factors (3-8). Various studies have indicated a significant genetic contribution to AMD risk (9). For example, it has been reported that advanced AMD is more prevalent in Caucasian populations as compared with other races that possess higher levels of uveal pigmentation and skin melanin (10). Furthermore, the population-attributed AMD risk related to genetic factors was 23% (11, 12). First-degree relatives of patients with late AMD developed the disease at an increased rate at a relatively young age (12, 13). The higher occurrence of AMD among monozygotic twins and first-degree relatives of AMD patients as compared with spouses and unrelated ...

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“…Absence or sparseness of eyelashes and eyebrows are also common in this syndrome (5) . Other, less common, ocular manifestations appear to include microphthalmia, lacrimal obliteration, keratoconus, corneal scleralization, pigment deposits on cornea and conjunctiva, coloboma atrophy in the iris and retina, chorioretinal atrophy, congenital glaucoma, and tilted optic discs (1,4,5,8) . This report presents two cases presenting with ocular surface findings uncharacteristic of RTS, including palpebral disease and conjunctival fibrotic process.…”

Section: Discussionmentioning

confidence: 97%

“…Previous reports have established bilateral cataracts, developing early in life, as the most common ocular lesion seen in RTS patients (3) , the prevalence of which varies between 5% and 73%, depending on the study (5) . Absence or sparseness of eyelashes and eyebrows are also common in this syndrome (5) .…”

Section: Discussionmentioning

confidence: 99%

Rothmund-Thomson syndrome and ocular surface findings: case reports and review of the literature

Miranda

Rivera-Monge

Farias³

2016

Arquivos Brasileiros De Oftalmologia

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Ocular Manifestations in the Inherited DNA Repair Disorders

Cited by 84 publications

References 123 publications

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

Cockayne Syndrome in Adults: Review With Clinical and Pathologic Study of a New Case

Synergic effect of polymorphisms inERCC65′ flanking region andcomplement factor Hon age-related macular degeneration predisposition

Rothmund-Thomson syndrome and ocular surface findings: case reports and review of the literature

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