Fragile X—A Family of Disorders: Changing Phenotype and Molecular Genetics



In 1938, Penrose noted a higher incidence of mental retardation (MR) in males and reports of families with only affected males (Penrose, A clinical and genetic study of 1,280 cases of mental defect. Special report series no. 229. Medical Research Council, London, 1938). These observations were compatible with X-linked inheritance, and numerous reports appeared in the literature (Howard-Peebles, J Ment Defic Res 26: 205–213, 1982). Based on this early work, a clinically nonspecific X-linked MR disorder was delineated and called Renpenning’s syndrome, Martin-Bell syndrome, or nonspecific X-linked MR. In 1959, Lubs described the first family with cytogenetic expression of the “marker X,” which became the fragile X (fraX), and the heterogeneity of this nonspecific X-linked MR disorder became apparent (Lubs, Am J Hum Genet 21: 231–244, 1969). Numerous disorders have been delineated from this original subgroup of MR males. The fraX subgroup was unique because there was a diagnostic laboratory test; the name Martin-Bell syndrome was attached when this family, first described in 1943, was shown to be positive for the fraX (Hamel et al, Am J Med Genet 94: 361–363, 2000), (Martin and Bell, J Neurol Psychiatry 6:154–157, 1943). However, the popular name for this disorder became fragile X syndrome (FXS).


Intelligence Quotient Trinucleotide Repeat Learn Disability Fragile Site FMR1 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author would like to thank Patricia N. Howard-Peebles, author of the chapter in previous editions, for providing the general scope and framework of the material.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.UCD DNA Diagnostic Laboratory, Department of PediatricsUniversity of Colorado School of MedicineAuroraUSA

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