A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from hismother and neurofibromatosis type 1 from his father

We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dysch ondrosteosis (LWD). His father had NF1. His mother had LWD plus additional findings of Turner syndrome (TS): high arched palate, bicuspid aortic valve , aortic stenosis, and premature ovarian failure. The proband's karyotype w as 46,Y.,dic(YY)(p22.3;p11.32). Despite having almost the same genetic cons titution as 47,XXY Klinefelter syndrome, he was normally virilized, althoug h slight elevation of serum gonadotropins indicated gonadal dysfunction. Hi s mother's karyotype was mosaic 45,X[17 cells]/46,Xdic(XY)(p22.3; p11.32)[3 cells].ish dic(YY)(DXZ1+,DYZ1+). The dic(Y.,Y) chromosome was also positiv e for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(XY) chr omosome was also positive for X markers DXZ1 and a sequence <300 kb from PA BX, suggesting that the deletion encompassed only pseudoautosomal sequences . Replication studies indicated that the normal X and the dic(Y,Y) were ran domly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenot ype was most likely due to 45,X mosaicism. This family segregating Mendelia n and chromosomal disorders illustrates extreme sex chromosome variation co mpatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, es pecially in patients with findings such as premature ovarian failure or aor tic abnormalities not associated with isolated SHOX haploinsufficiency. (C) 2001 Wiley-Liss, Inc.