Histopathology of the Eye in Cockayne's Syndrome

Levin, Peter S.; Green, W. Richard; Victor, David I.; MacLean, Angus L.

doi:10.1001/archopht.1983.01040020095016

Cited by 35 publications

(20 citation statements)

References 31 publications

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“…Many articles contain explicit statements about the severity of a case, such as using the words severe or mild or atypical to describe a patient. Examples include, but are not limited to [Kennedy et al, 1980;Nishio et al, 1988;Lahiri and Davies, 2003] other articles made a patient's severity group clear in spite of not using explicit terms [Levin et al, 1983;Tinsa et al, 2009;Jaakkola et al, 2010]. Information that made a patient's severity group clear included photographs, data related to length-or heightfor-age and head circumference, and descriptions of a patient's skills and abilities.…”

Section: Severity Group Classificationssupporting

confidence: 45%

“…None was able to combine two words, recognize letters, or write. These findings are consistent with the literature [Riggs and Seibert, 1972;Levin et al, 1983;Leech et al, 1985;Nishio et al, 1988;Patton et al, 1989;Hayashi et al, 1992;Bender et al, 2003]. Parents reported that their children created non-verbal ways of expressing needs, such as tapping a leg to indicate needing a blanket.…”

Section: Severe Cssupporting

confidence: 42%

“…Kyphosis was reported in 12 patients in this group; it also inhibited gross motor skill development. Observations about inability to sit or walk in severely affected CS patients have also been reported in the literature [Hallervorden, 1950;Lowry et al, 1971;Levin et al, 1983;Nishio et al, 1988;Jaeken et al, 1989;Bender et al, 2003;Sonmez et al, 2006;Laugel et al, 2008b].…”

Section: Severe Cssupporting

confidence: 40%

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A comprehensive description of the severity groups in Cockayne syndrome

Natale¹

2011

American J of Med Genetics Pt A

104

109

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Cockayne syndrome (CS) is a rare degenerative disorder with a common set of symptoms but a very wide variation in phenotype. The variation is sufficiently wide that CS patients have traditionally been described in three different severity groups. Unfortunately, there is no single source for information about the different severity groups. This problem can complicate not only diagnosis, but accurate prognosis as well. The goal of this study was to describe the phenotypic variation in CS as completely as possible. This article provides extensive descriptions of traits common to each group and their degree of severity in each group. Forty-five people with CS were surveyed and information from the published literature was used to increase the sample sizes for calculations. This study provides new information, including statistical data for each of the three severity groups (mean age at death, average head circumference, and average length or stature). The study includes cerebro-oculo-facial syndrome (COFS) as a severe form of CS, based on results of recently published genetic studies performed by other authors. This study proposes revised names for CS severity groups: severe, moderate, and mild. The groups were formerly called Type II/early onset CS, Type I/classical CS, and Type III/atypical/mild/late-onset CS, respectively. A fourth newly documented group, UV sensitivity only/adult onset, is also described. Average ages of death were calculated as 5.0 years (severe), 16.1 years (moderate), and 30.3 years (mild).

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Section: Severity Group Classificationssupporting

confidence: 45%

Section: Severe Cssupporting

confidence: 42%

Section: Severe Cssupporting

confidence: 40%

See 1 more Smart Citation

A comprehensive description of the severity groups in Cockayne syndrome

Natale¹

2011

American J of Med Genetics Pt A

104

109

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“…However, case reports with detailed morphological data on CS eye pathology are scarce (38). To our knowledge, the literature contains only one report on a 44-month-old boy documenting loss of photoreceptors, in addition to other pathological changes such as ganglion cells and nerve fiber loss, and irregular RPE pigmentation (29). We have shown here that, similar to this patient, Csb m/m mice undergo spontaneous retinal degeneration, which consists of a gradual loss of rods with age.…”

Section: Discussionsupporting

confidence: 44%

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

Gorgels

Pluijm

Brandt

et al. 2007

Molecular and Cellular Biology

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Mutations in the CSB gene cause Cockayne syndrome (CS), a DNA repair disorder characterized by UV sensitivity and severe physical and neurological impairment. CSB functions in the transcription-coupled repair subpathway of nucleotide excision repair. This function may explain the UV sensitivity but hardly clarifies the other CS symptoms. Many of these, including retinopathy, are associated with premature aging. We studied eye pathology in a mouse model for CS. Csb m/m mice were hypersensitive to UV light and developed epithelial hyperplasia and squamous cell carcinomas in the cornea, which underscores the importance of transcriptioncoupled repair of photolesions in the mouse. In addition, we observed a spontaneous loss of retinal photoreceptor cells with age in the Csb m/m retina, resulting in a 60% decrease in the number of rods by the age of 18 months. Importantly, when Csb m/m mice (as well as Csa ؊/؊ mice) were exposed to 10 Gy of ionizing radiation, we noticed an increase in apoptotic photoreceptor cells, which was not observed in wild-type animals. This finding, together with our observation that the expression of established oxidative stress marker genes is upregulated in the Csb m/m retina, suggests that (endogenous) oxidative DNA lesions play a role in this CS-specific premature-aging feature and supports the oxidative DNA damage theory of aging.

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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: 46%

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.

101

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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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Histopathology of the Eye in Cockayne's Syndrome

Cited by 35 publications

References 31 publications

A comprehensive description of the severity groups in Cockayne syndrome

A comprehensive description of the severity groups in Cockayne syndrome

Retinal Degeneration and Ionizing Radiation Hypersensitivity in a Mouse Model for Cockayne Syndrome

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

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