This page was produced as an assignment for Genetics 564 an undergraduate capstone course at UW-Madison.
ERCC6 and Cockayne Syndrome Type IIThe ERCC6 gene is found on the long arm of chromosome 10 at position 11.23 [2]. The mutations in this gene that cause CS are rare, and are passed in an autosomal recessive inheritance pattern. ERCC6 (protein product CSB) and a similar gene called ERCC8 (protein product CSA) both assist in recognizing and repairing DNA lesions during transcription. CSB resides in the nucleus, while CSA is recruited by CSB from the cytoplasm into the nucleus when damaged DNA is detected, along with other downstream nucleotide excision repair proteins [8]. Once inside the nucleus, CSA polyubiquitinates CSB, removing it from the DNA lesion and allowing nucleotide excision repair mechanisms to take over and fix the DNA [9]. Much of this damaged DNA is a result of UV exposure, which explains why mutations in ERCC6 that knock out CSB function lead to extreme photosensitivity, one of the most common symptoms of Cockayne Syndrome.
Although it is not clear exactly how altercations to the CSA and CSB proteins and the TC-NER pathway cause the CS phenotype, it is estimated that approximately 70% of CS affected individuals have mutations in the ERCC6 gene [7]. There are at least 61 distinct mutations found in the ERCC6 gene of individuals with defective CSB [8]. Types of Cockayne SyndromeCockayne Syndrome has four distinct phenotypic classifications. These four types are Cockayne Syndrome Type I, Cockayne Syndrome Type II, Cockayne Syndrome Type III, and Xeroderma pigmentosum-Cockayne Syndrome. Individuals with CS Type I, also known as the “classic”, more moderate form of CS, experience progressively worsening symptoms after about a year. Affected individuals undergo normal prenatal growth, but growth and developmental abnormalities become apparent by the end of the second year of life [5]. Individuals with CS Type II, known as the most severe variant of CS, show symptoms of CS at birth, and experience very little postnatal neurological development [5]. CS Type III is characterized by normal postnatal development with symptoms developing at a later time than expected in an individual with CS Type I [5]. XP-CS phenotype is more complicated in that it includes characteristics of Xeroderma pigmentosum as well as CS, but often does not display the full extent of either condition [5].
Symptoms of Cockayne Syndrome
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Support Networks and Foundations
Share & Care Cockayne Syndrome Network
P.O. Box 282 Waterford, VA 20197 Phone: 703-727-0404 (Executive Director's Phone Number) Email: [email protected] http://cockaynesyndrome.org/ |
Children Living With Inherited Metabolic Diseases (CLIMB)
Phone: 0800-652-3181 Email: [email protected] http://www.climb.org.uk/ |
Genetic and Rare Disease Information Center (GARD)
P.O. Box 8126 Gaithersburg, MD 20898-8126 Phone: 1-888-205-2311 https://rarediseases.info.nih.gov/ |
References
[1] Vermeulen, W., Fousteri, M. 2013. Mammalian transcription-coupled excision repair. Cold Spring Harb. Perspect. Biol. 5: a012625.
[2] ERCC6 Gene: Genetics Home Reference. https://ghr.nlm.nih.gov/gene/ERCC6#conditions
[3] Cockayne Syndrome: National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/cockayne-syndrome/
[4] Cockayne Syndrome: Genetics Home Reference. https://ghr.nlm.nih.gov/condition/cockayne-syndrome#inheritance
[5] Laugel V. 2000. Cockayne Syndrome. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1342/
[6] Rapin, I., Lindenbaum, Y., Dickson, D.W., Kraemer, K.H., Robbins, J.H. 2000. Cockayne syndrome and xeroderma pigmentosum. Neurobiology, 55(10): 1442-`1449.
[7] Wilson, B. T., Stark, Z., Sutton, R. E., Danda, S., Ekbote, A. V., Elsayed, S. M., … Wilson, I. J. 2016. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genetics in Medicine, 18(5), 483–493. http://doi.org/10.1038/gim.2015.110
[8] Laugel, V., Dalloz, C., Durand, M. et al. 2010. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum. Mutat., 31: 113–126. doi:10.1002/humu.21154
[9] Wilson, B., T., Lochan, A., Stark, Z., Sutton, R. E. 2016. Novel missense mutations in a conserved loop between ERCC6 (CSB) helicase motifs V and VI: Insights into Cockayne syndrome. Am. J. Med. Gen. 170(3), 773-776. 10.1002/ajmg.a.37501
Images and Videos
Youtube video channel: CockayneSyndromeAF
Cover image: http://www.healthline.com/health-news/genetic-causes-of-bipolar-disorder
Four panel picture: http://cockaynesyndrome.org/
TC-NER: http://www.acsu.buffalo.edu/~kowalsk/dnarepair/ner.html
Microcephaly: http://mytips10.blogspot.com/2016/01/microcephaly-definition-what-is-microcephaly.html
Cataract: http://www.fleye.com/cataract-center/cataract-faqs/
Autosomal Recessive: http://disorders.eyes.arizona.edu/disorders/cockayne-syndrome-type-ii
Gene and Protein Structure: http://www.nature.com/nrg/journal/v10/n11/fig_tab/nrg2663_F2.html
This website was created for Genetics 564 by Zachary Beethem, an undergraduate genetics major at UW-Madison.
He can be reached via email: [email protected]
Date of last website update: April 2017
[1] Vermeulen, W., Fousteri, M. 2013. Mammalian transcription-coupled excision repair. Cold Spring Harb. Perspect. Biol. 5: a012625.
[2] ERCC6 Gene: Genetics Home Reference. https://ghr.nlm.nih.gov/gene/ERCC6#conditions
[3] Cockayne Syndrome: National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/cockayne-syndrome/
[4] Cockayne Syndrome: Genetics Home Reference. https://ghr.nlm.nih.gov/condition/cockayne-syndrome#inheritance
[5] Laugel V. 2000. Cockayne Syndrome. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1342/
[6] Rapin, I., Lindenbaum, Y., Dickson, D.W., Kraemer, K.H., Robbins, J.H. 2000. Cockayne syndrome and xeroderma pigmentosum. Neurobiology, 55(10): 1442-`1449.
[7] Wilson, B. T., Stark, Z., Sutton, R. E., Danda, S., Ekbote, A. V., Elsayed, S. M., … Wilson, I. J. 2016. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genetics in Medicine, 18(5), 483–493. http://doi.org/10.1038/gim.2015.110
[8] Laugel, V., Dalloz, C., Durand, M. et al. 2010. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum. Mutat., 31: 113–126. doi:10.1002/humu.21154
[9] Wilson, B., T., Lochan, A., Stark, Z., Sutton, R. E. 2016. Novel missense mutations in a conserved loop between ERCC6 (CSB) helicase motifs V and VI: Insights into Cockayne syndrome. Am. J. Med. Gen. 170(3), 773-776. 10.1002/ajmg.a.37501
Images and Videos
Youtube video channel: CockayneSyndromeAF
Cover image: http://www.healthline.com/health-news/genetic-causes-of-bipolar-disorder
Four panel picture: http://cockaynesyndrome.org/
TC-NER: http://www.acsu.buffalo.edu/~kowalsk/dnarepair/ner.html
Microcephaly: http://mytips10.blogspot.com/2016/01/microcephaly-definition-what-is-microcephaly.html
Cataract: http://www.fleye.com/cataract-center/cataract-faqs/
Autosomal Recessive: http://disorders.eyes.arizona.edu/disorders/cockayne-syndrome-type-ii
Gene and Protein Structure: http://www.nature.com/nrg/journal/v10/n11/fig_tab/nrg2663_F2.html
This website was created for Genetics 564 by Zachary Beethem, an undergraduate genetics major at UW-Madison.
He can be reached via email: [email protected]
Date of last website update: April 2017