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Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 367--368

Worldwide Studies on Cockayne Syndrome are Needed

Vilhelm A Bohr 
 National Institute on Aging, National Institutes of Health, USA

Correspondence Address:
Vilhelm A Bohr
National Institute on Aging, National Institutes of Health

How to cite this article:
Bohr VA. Worldwide Studies on Cockayne Syndrome are Needed.Neurol India 2021;69:367-368

How to cite this URL:
Bohr VA. Worldwide Studies on Cockayne Syndrome are Needed. Neurol India [serial online] 2021 [cited 2021 Jun 24 ];69:367-368
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This commentary is associated with the paper in this volume by Phadke, et al. Clinical and mutation spectra of Cockayne syndrome in India.[1]

Cockayne syndrome (CS) is a rare, neurodegenerative disease associated with cachectic dwarfism, visual and hearing problems, retarded growth and many other features.[2] The classic clinical study was Nance and Berry, 1992[3], and there have been several since. Comparing the study by Wilson et al., 2015[4] with (3), the most prevalent clinical features are growth retardation, hearing loss, cataracts, and retinal dystrophy. There have been several clinical studies in the West and Japan, and it is now very important to expand to other countries such as India, to gain better insight into the clinical features and prevalence around the world. It is generally considered that the prevalence is 2.5 cases per million, but we need increased insight into the worldwide distribution and mutational spectrum of this disease. CS patients have distinct features and appearance that resemble normal aging, and the disorder is considered a premature aging or progeroid disease.[2] Thus, insight into the underlying mechanism of this disease may have important implications for understanding the aging process, which is a worldwide priority and has attracted research on CS. CS has two genotypes, CSA and CSB, and the clinical features of these two complementation groups are similar, although CSA is usually less severe. That is not the case in the current study[1], where the single CSA case is rather severe. Interestingly, while the CSA and CSB proteins both are involved in DNA repair, transcription and mitochondrial functions[5], they have different and distinct functions and activities. It is of interest to understand where in DNA metabolism the function of the CSA and CSB proteins coordinate. One such area is the mitochondrial function , and there is increased awareness that CS is associated with mitochondrial dysfunction. The severe neurodegeneration in CS may at least in part be due to this mitochondrial dysfunction in the form of decreased mitophagy, which is the ability to dispose of dysfunctional mitochondria.[5]

This notion is supported by a recent study[6] that demonstrates that NAD supplementation, which enhances mitochondrial function (mitophagy) and DNA repair can greatly reduce hearing loss in mice with CSA and CSB. Since there is no available treatment currently for this severe disease, it is likely that interventions may become available in the future. While CS is a very rare disease, it is very important to study it from both a clinical and mechanistic viewpoint. It is very welcome to see a study from India on this disease, and it is hoped that this will lead to more Indian studies and increased cooperation between researchers and patient groups worldwide. Organized patient groups exist in the US and Japan, and it is of great value to have patient organizations in other countries coordinate this effort worldwide to help and advise families regarding how to deal with the challenges of having children with CS.


1Narayanan DL, Tuteja M, McIntyre AD, Hegele RA, Calmels N, Obringer C, et al. Clinical and Mutation Spectra of Cockayne Syndrome in India. Neurol India 2021;69:362-6.
2Karikkineth AC, Scheibye-Knudsen M, Fivenson E, Croteau DL, Bohr VA. Cockayne syndrome: Clinical features, model systems and pathways. Ageing Res Rev 2017;33:3-17.
3Nance MA, Berry SA. Cockayne syndrome: Review of 140 cases. Am J Med Genet 1992;42:68-84.
4Wilson BT, Stark Z, Sutton RE, Danda S, Ekbote AV, Elsayed SM, et al. The Cockayne Syndrome Natural History (CoSyNH) study: Clinical findings in 102 individuals and recommendations for care. Genet Med 2016;18:483-93.
5Tiwari V, Baptiste BA, Okur MN, Bohr VA. Current and emerging roles of Cockayne syndrome group B (CSB) protein. Nucleic Acids Res 2021;[Online ahead of print].
6Okur MN, Mao B, Kimura R, Haraczy S, Fitzgerald T, Edwards-Hollingsworth K, et al. Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome. NPJ Aging Mech Dis 2020;6:1.