47,XXX male: A clinical and molecular study

We report a 53-year-old Japanese male with a 47,XXX karyotype, His clinical features included hypoplastic scrotal testes (4 ml bilaterally), normally formed small penis (3.8 cm), relatively poor pubic hair development (Tanner stage 3), gynecomastia, age-appropriate male height (159.1 cm), and mental retardation (verbal IQ of 56), Serum testosterone was markedly reduced (0. 6 nmol/L), A needle biopsy showed severe testicular degeneration. FISH anal ysis revealed complex mosaicism consisting of (1) 47,XXX cells with a singl e copy of SRY (n=177), two copies of SRY (n=3), and no SRY (n=1); (2) 46,XX cells with a single copy of SRY (n=9) and no SRY (n=3); (3) 45,X cells wit h no SRY (n=5); and (4) 48,XXXX cells with a single copy of SRY (n=1) and t wo copies of SRY (n=1), PCR analysis showed the presence of Yp portion with the breakpoint between DYS264 and AMELY, Microsatellite analysis demonstra ted three alleles for DMD and AR. X-inactivation analysis for the methylati on status of the AR gene showed random inactivation of the three X chromoso mes, The results suggest that this 47,XXX male has resulted from abnormal X Y interchange during paternal meiosis and X-X nondisjunction during materna l meiosis. Complex mosaicism may be due to the age-related increase in mito tic nondisjunction which is prone to occur in rapidly dividing lymphocytes and to the presence of two randomly inactivated X chromosomes which may beh ave asynchronously during mitosis, and clinical features of this male would primarily be explained by the genetic information on the SRY (+) der(X) ch romosome and his advanced age. (C) 2001 Wiley-Liss, Inc.