PMC:1852721 / 34633-37398 JSONTXT

{"project":"2_test","denotations":[{"id":"17357067-2391361-2054052","span":{"begin":2402,"end":2408},"obj":"2391361"},{"id":"17357067-8406501-2054053","span":{"begin":2439,"end":2441},"obj":"8406501"}],"text":"“The Lessons of Rare Maladies”\nIn 1956, I dedicated the first edition of my Heritable Disorders of Connective Tissue 21 to Archibald Garrod “and to all who believe, as he did, that the clinical investigation of hereditary disorders can shed light on normal developmental and biochemical mechanisms.” (The dedication was accompanied by a previously unpublished etching of Garrod in academic garb by T. Binney Gibbs [created in 1922]. This was provided to me by Garrod’s daughter, distinguished Cambridge University archeologist Dorothy A. E. Garrod.) The preface of Heritable Disorders of Connective Tissue reproduced the now-well-known quotation from a letter written (in Latin) by William Harvey in 1657 that Garrod included (in translation) in his paper entitled “The lessons of rare maladies” published in Lancet in 192831:\nNature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature by careful investigation of cases of rarer forms of disease. For it has been found, in almost all things, that what they contain of useful or applicable nature is hardly perceived unless we are deprived of them, or they become deranged in some way.\nThis Harveian/Garrodian principle has been extensively documented in the case of rare genetic syndromes. The many rare disorders cataloged in OMIM are “experiments of nature” with much to teach about normal biochemical, developmental, and physiologic mechanisms, and indeed much has been learned from them, especially in the 20+ years since the first “disease gene” identified by positional cloning was recorded in OMIM.\nIncreasingly, basic scientists turn to the human for exploration of the significance of findings in experimental systems or look for “human models” of phenotypes or phenomena in Caenorhabditis elegans, Drosophila, mouse, and other experimental species. The researcher asks, “Has a defect related to ‘my' gene or protein been identified in the human?” OMIM has proved a useful way to find human models of “disorders” in experimental organisms.\nA human-interest story in this connection involves the late Robert J. Gorlin (1923–2006) and his son Jed B. Gorlin. Jed cloned the filamin A gene (FLNA [MIM +300017]) in 199032 and mapped it to Xq28 in 1993.33 It was of particular delight to his father when FLNA was found (by others) to be the site of mutations underlying frontometaphyseal dysplasia (FMD [MIM #305620]), otopalatodigital syndrome (OPD1 [MIM #311300]), and several other disorders for which the father had provided definitive clinical descriptions as well as names."}