Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome

M. V. Bell; M. C. Hirst; Y. Nakahori; R. N. MacKinnon; A. Roche; T. J. Flint; P. A. Jacobs; N. Tommerup; L. Tranebjaerg; U. Froster-Iskenius; B. Kerr; G. Turner; R. H. Lindenbaum; R. Winter; M. Prembrey; S. Thibodeau; K. E. Davies

doi:10.1016/0092-8674(91)90514-Y

Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome

M. V. Bell, M. C. Hirst, Y. Nakahori, R. N. MacKinnon, A. Roche, T. J. Flint, P. A. Jacobs, N. Tommerup, L. Tranebjaerg, U. Froster-Iskenius, B. Kerr, G. Turner, R. H. Lindenbaum, R. Winter, M. Prembrey, S. Thibodeau, K. E. Davies

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

264 Scopus citations

Abstract

The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdisected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.

Original language	English (US)
Pages (from-to)	861-866
Number of pages	6
Journal	Cell
Volume	64
Issue number	4
DOIs	https://doi.org/10.1016/0092-8674(91)90514-Y
State	Published - Feb 22 1991

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/0092-8674(91)90514-Y

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Bell, M. V., Hirst, M. C., Nakahori, Y., MacKinnon, R. N., Roche, A., Flint, T. J., Jacobs, P. A., Tommerup, N., Tranebjaerg, L., Froster-Iskenius, U., Kerr, B., Turner, G., Lindenbaum, R. H., Winter, R., Prembrey, M., Thibodeau, S., & Davies, K. E. (1991). Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome. Cell, 64(4), 861-866. https://doi.org/10.1016/0092-8674(91)90514-Y

Bell, MV, Hirst, MC, Nakahori, Y, MacKinnon, RN, Roche, A, Flint, TJ, Jacobs, PA, Tommerup, N, Tranebjaerg, L, Froster-Iskenius, U, Kerr, B, Turner, G, Lindenbaum, RH, Winter, R, Prembrey, M, Thibodeau, S & Davies, KE 1991, 'Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome', Cell, vol. 64, no. 4, pp. 861-866. https://doi.org/10.1016/0092-8674(91)90514-Y

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title = "Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome",

abstract = "The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdisected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.",

author = "Bell, {M. V.} and Hirst, {M. C.} and Y. Nakahori and MacKinnon, {R. N.} and A. Roche and Flint, {T. J.} and Jacobs, {P. A.} and N. Tommerup and L. Tranebjaerg and U. Froster-Iskenius and B. Kerr and G. Turner and Lindenbaum, {R. H.} and R. Winter and M. Prembrey and S. Thibodeau and Davies, {K. E.}",

note = "Funding Information: have contributed to the collection and typing of families. We thank Mark McKinley for PFG blocks of affected males and Bryan Bolton (PHLS, Porton Down) for cell lines. We are grateful to Grant Sutherland for probe VK.21 and Niklaus Dahl for U6.2. This research was funded by the Medical Research Council of Great Britain and Action Research for the Crippled Child.",

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T2 - Hypermethylation and clinical expression of the fragile X syndrome

AU - Bell, M. V.

AU - Hirst, M. C.

AU - Nakahori, Y.

AU - MacKinnon, R. N.

AU - Roche, A.

AU - Flint, T. J.

AU - Jacobs, P. A.

AU - Tommerup, N.

AU - Tranebjaerg, L.

AU - Froster-Iskenius, U.

AU - Kerr, B.

AU - Turner, G.

AU - Lindenbaum, R. H.

AU - Winter, R.

AU - Prembrey, M.

AU - Thibodeau, S.

AU - Davies, K. E.

N1 - Funding Information: have contributed to the collection and typing of families. We thank Mark McKinley for PFG blocks of affected males and Bryan Bolton (PHLS, Porton Down) for cell lines. We are grateful to Grant Sutherland for probe VK.21 and Niklaus Dahl for U6.2. This research was funded by the Medical Research Council of Great Britain and Action Research for the Crippled Child.

PY - 1991/2/22

Y1 - 1991/2/22

N2 - The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdisected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.

AB - The most common genetic cause of mental retardation after Down's syndrome, the fragile X syndrome, is associated with the occurrence of a fragile site at Xq27.3. This X-linked disease is intriguing because transmission can occur through phenotypically normal males. Theories to explain this unusual phenomenon include genomic rearrangements and methylation changes associated with a local block of reactivation of the X chromosome. Using microdisected markers close to the fragile site, we have been able to test these hypotheses. We present evidence for the association of methylation with the expression of the disease. However, there is no simple relationship between the degree of methylation and either the level of expression of the fragile site or the severity of the clinical phenotype.

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Physical mapping across the fragile X: Hypermethylation and clinical expression of the fragile X syndrome

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