A DUPLICATION OF DISTAL XP ASSOCIATED WITH HYPOGONADOTROPIC HYPOGONADISM, HYPOPLASTIC EXTERNAL GENITALIA, MENTAL-RETARDATION, AND MULTIPLE CONGENITAL-ABNORMALITIES

An unusual familial case of three sibs with a partial duplication of d istal Xp sequences is described. The proband, an 18 year old boy, show ed mental retardation, severe dysmorphic features, hypogonadotrophic h ypogonadism (HHG), and hypoplastic external genitalia. His karyotype w as 46,Y,inv dup(X)(p22.11-->p22.32). The proband has two sisters each with the same inv dup(Xp) chromosome. Both sisters presented with shor t stature but were otherwise phenotypically normal. The abnormal X chr omosome was inactive in the majority of cells examined. Southern blot dosage analysis indicated a duplication of distal Xp sequences. The pr oximal breakpoint is located between DXS28 and DXS41, and is therefore at least 2 Mb distal to the DSS locus. The relationship between the p henotype and the Xp duplication is discussed.