Cockayne syndrome

Disorders of nucleotide excision repair [DS:H00403]

Cockayne syndrome (CS) is a rare recessive disorder characterized by progressive multisystem abnormalities such as postnatal growth deficiency, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries and neurological degeneration. CS has thus been classified as a segmental premature-aging syndrome. CSA caused by mutation in the gene encoding the group 8 excision-repair cross-complementing protein (ERCC8) is early childhood onset in the second year of life, CSB caused by mutation in the ERCC6 gene is late childhood onset with mild symptoms. ERCC8 encodes a Walker domain (WD)-repeat protein involved in the transcription-coupled repair system of the actively transcribed DNA. ERCC6 protein is at the interface of transcription and DNA repair and is involved in transcription-coupled and global genome-DNA repair, as well as in general transcription.

Neurodegenerative disease

(CSA) ERCC8; Excision repair cross complementing, group 8 (mutation) [HSA:1161] [KO:K10570]
(CSB) ERCC6; Excision repair cross complementing, group 6 (mutation) [HSA:2074] [KO:K10841]

Affected region: cerebral cortex, cerebellum, basal ganglia
Microscopic lesion: accumulate of DNA lesions, tigroid-type demyelination, multifocal calcium deposition

PMID:17603927

Frosina G.

The current evidence for defective repair of oxidatively damaged DNA in Cockayne syndrome.

Free Radic Biol Med 43:165-77 (2007)
DOI:10.1016/j.freeradbiomed.2007.04.001

PMID:17084038

Kleppa L, Kanavin OJ, Klungland A, Stromme P

A novel splice site mutation in the Cockayne syndrome group A gene in two siblings with Cockayne syndrome.

Neuroscience 145:1397-406 (2007)
DOI:10.1016/j.neuroscience.2006.09.025

PMID:14639525 (CSB)

Licht CL, Stevnsner T, Bohr VA

Cockayne syndrome group B cellular and biochemical functions.

Am J Hum Genet 73:1217-39 (2003)
DOI:10.1086/380399

PMID:9443879 (CSB)

Mallery DL, Tanganelli B, Colella S, Steingrimsdottir H, van Gool AJ, Troelstra C, Stefanini M, Lehmann AR

Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome.

Am J Hum Genet 62:77-85 (1998)
DOI:10.1086/301686

PMID:7664335 (CSA)

Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC

The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH.

Cell 82:555-64 (1995)
DOI:10.1016/0092-8674(95)90028-4