Letter to in Norma
To the Editor: the Editor: Fragile X Chromosome Males I found the recent report by Hecht, Jacky, and Sutherland [1982] on the Fragile X Chromosome Workshop (Jerusalem, September 198 1) particularly interesting and a good summary, it seems, of the present situation. However, I must take exception to one particular point of the discussion (p 493), namely, that which concerns the presence of a fragile X in two normal males, reported by myself and colleagues in the Lancet [1981]. By position and appearance on an identified X chromosome the males in question had a fragile X. (It so happens that Dr. Sutherland has since visited our laboratory and is in a position to confirm this finding.) That the two males were behaviourally and intellectually normal was also clear. A collective reaction of surprise is understandable, but one of doubt, let alone "considerable doubt," is not what I would anticipate from a scientific gathering of this nature. Furthermore, we are told that these feelings of doubt were deepened by Sutherland's failure to find a fragile X among a thousand normal neonates he examined. No matter how many neonates have been examined with negative results, our incontrovertible findings remain, and the simplest explanation of these is that the fragile X may occasionally be compatible wth mental normality in the male.
Possibly the Workshop might have taken a less dubious view of our report had they known at the time of the family reported by Webb and his colleagues [1981], stemming from a male carrier of the fragile X, who was unremarkable, apart from an unusual personality attributed to war neurosis. Again, evidence from other family studies clearly indicates that our findings should not be dismissed too lightly. Nielsen et a1 [1981] report a large pedigree showing transmission through apparently unaffected males, while Richards et a1 [ 19811, in their recent reinvestigation of the original Martin-Bell family, remind us that in this case all affected subjects are derived from two normal brothers and their normal sister. We do not, of course, know whether these unaffected males showed a fragile site, but families such as these show that the pattern of inheritance and phenotypic expression is not always straightforward.