Normal Pressure Hydrocephalus

Brumback, Roger A.

doi:10.1001/archneur.1978.00500300011002

Cited by 67 publications

(9 citation statements)

References 31 publications

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“…A different patient carrying a homozygous missense mutation in the same domain was reported to have low RRS, but this was associated with a more severe type I clinical phenotype (patient 08STR2 [ 25 ]). In the few previously reported cases of mild late-onset CS, decreased RRS has always been an associated finding [ 25 , 45 , 61 – 69 ]. However, the classical diagnostic procedure for CS usually recommends performing molecular sequencing only after identification of a functional defect in the RRS, and thus atypical CS patients with normal or inconclusive RRS may be missed.…”

Section: Discussionmentioning

confidence: 99%

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Calmels

Greff

Obringer

et al. 2016

Orphanet J Rare Dis

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BackgroundDeficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS).MethodsOur test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies).ResultsWe identified causative mutations in 17 out of the 40 patients (43 %). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes.ConclusionsOur study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0408-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Calmels

Greff

Obringer

et al. 2016

Orphanet J Rare Dis

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“…20,70 While Cockayne syndrome also presents with photosensitivity and neurologic dysfunction, patients tend to have a “bird-like” face, microcephaly, premature aging, dwarfism, cachexia, sunken eyes, and usually die before age 30. 10,54 Though the genetic defects are closely related, these diseases have a different systemic and ocular manifestations. 20 …”

Section: Literature Review and Discussionmentioning

confidence: 99%

Ophthalmic Manifestations and Histopathology of Xeroderma Pigmentosum: Two Clinicopathological Cases and a Review of the Literature

Ramkumar

Brooks

Cao

et al. 2011

Survey of Ophthalmology

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Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the UV exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two Caucasian women who had xeroderma pigmentosum with neurological degeneration: Case 1, who died at age 44 and Case 2, who died at age 45. Case 1 with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun protected and had 3 skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus and exposure keratopathy. Case 1 had bilateral optic atrophy, while Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina.

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“…a deficiency in DNA excision repair, as measured by unscheduled DNA synthesis, and are unable to repair most types of UV-induced DNA photoproducts (3). In CS cells, however, unscheduled DNA synthesis is normal (12)(13)(14) and removal ofphotoproducts from the genome overall is normal, while repair of cyclobutane dimers from actively transcribed genes is reduced compared to normal cells (15).…”

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confidence: 99%

Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal.

Parris

Kraemer

1993

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

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We compared the contribution to mutagenesis in Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repairdeficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally reduced and mutation frequency was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of >200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, our data suggest that prevention of UV-induced skin cancers is associated with proficient repair of nondimer photoproducts.

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Normal Pressure Hydrocephalus

Cited by 67 publications

References 31 publications

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Ophthalmic Manifestations and Histopathology of Xeroderma Pigmentosum: Two Clinicopathological Cases and a Review of the Literature

Ultraviolet-induced mutations in Cockayne syndrome cells are primarily caused by cyclobutane dimer photoproducts while repair of other photoproducts is normal.

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