01987nas a2200373   4500000000100000008004100001260001300042653003100055653001100086653002000097653003800117653001300155653001700168653001100185653001200196653000900208653001300217653001400230653003200244100001300276700001400289700001900303700001300322700001500335700001100350700001300361245012000374856006200494300001000556490000600566050001400572520101300586022001401599       2003                            d  c2003 Jan10aChromosomes, Human, Pair 610aFemale10aGenetic Linkage10aGenetic Predisposition to Disease10agenotype10aHLA Antigens10aHumans10aleprosy10aMale10aPedigree10aPhenotype10aTumor Necrosis Factor-alpha1 aMira M T1 aAlcaïs A1 aPietrantonio T1 aThuc N V1 aPhuong M C1 aAbel L1 aSchurr E00aSegregation of HLA/TNF region is linked to leprosy clinical spectrum in families displaying mixed leprosy subtypes.  uhttp://www.nature.com/gene/journal/v4/n1/pdf/6363911a.pdf  a67-730 v4  aMIRA 20033 a<p>Each year an estimated 600000 new leprosy cases are diagnosed worldwide. The spectrum of the disease varies widely from limited tuberculoid forms to extensive lepromatous forms. A measure of the risk to develop lepromatous forms of leprosy is provided by the extent of skin reactivity to lepromin (Mitsuda reaction). To address a postulated oligogenic control of leprosy pathogenesis, we investigated in the present study linkage of leprosy susceptibility, leprosy clinical subtypes, and extent of the Mitsuda reaction to six chromosomal regions carrying known or suspected leprosy susceptibility loci. The only significant result obtained was linkage of leprosy clinical subtype to the HLA/TNF region on human chromosome 6p21 (P(corrected)=0.00126). In addition, we established that within the same family different HLA/TNF haplotypes segregate into patients with different leprosy subtypes directly demonstrating the importance of this genome region for the control of clinical leprosy presentation.</p>  a1466-4879