Fragile X—A family of disorders: Changing phenotype and molecular genetics

Abstract

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 nonspeci fi c X-linked MR disorder was delineated and called Renpenning's syndrome, Martin-Bell syndrome, or nonspeci fi c X-linked MR. In 1959, Lubs described the fi rst family with cytogenetic expression of the “marker X,” which became the fragile X (fraX), and the heterogeneity of this nonspeci fi c 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, fi rst 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).