TY - JOUR
T1 - A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father
AU - Wei, Fanglin
AU - Cheng, Sou
AU - Badie, Nicole
AU - Elder, Frederick
AU - Scott, Charles
AU - Nicholson, Linda
AU - Ross, Judith L.
AU - Zinn, Andrew R.
PY - 2001/9/1
Y1 - 2001/9/1
N2 - We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (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 was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY Klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3; p11.32)[3 cells].ish dic(X;Y)(DXZ1+,DYZ1+). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence <300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.
AB - We report on a man with neurofibromatosis type 1 (NF1) and Leri-Weill dyschondrosteosis (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 was 46,X,dic(X;Y)(p22.3;p11.32). Despite having almost the same genetic constitution as 47,XXY Klinefelter syndrome, he was normally virilized, although slight elevation of serum gonadotropins indicated gonadal dysfunction. His mother's karyotype was mosaic 45,X[17 cells]/46,X,dic(X;Y)(p22.3; p11.32)[3 cells].ish dic(X;Y)(DXZ1+,DYZ1+). The dic(X;Y) chromosome was also positive for Y markers PABY, SRY, and DYZ5, but negative for SHOX. The dic(X;Y) chromosome was also positive for X markers DXZ1 and a sequence <300 kb from PABX, suggesting that the deletion encompassed only pseudoautosomal sequences. Replication studies indicated that the normal X and the dic(X;Y) were randomly inactivated in the proband's lymphocytes. LWD in the proband and his mother was explained by SHOX haploinsufficiency. The mother's female phenotype was most likely due to 45,X mosaicism. This family segregating Mendelian and chromosomal disorders illustrates extreme sex chromosome variation compatible with normal male and female sexual differentiation. The case also highlights the importance of karyotyping for differentiating LWD and TS, especially in patients with findings such as premature ovarian failure or aortic abnormalities not associated with isolated SHOX haploinsufficiency.
KW - Leri-Weill dyschondrosteosis
KW - Mosaicism
KW - Pseudoautosomal region
KW - SHOX
KW - SRY
KW - Sex chromosome abnormalities
KW - Turner syndrome
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UR - http://www.scopus.com/inward/citedby.url?scp=0035451571&partnerID=8YFLogxK
U2 - 10.1002/1096-8628(20010901)102:4<353::AID-AJMG1481>3.0.CO;2-7
DO - 10.1002/1096-8628(20010901)102:4<353::AID-AJMG1481>3.0.CO;2-7
M3 - Article
C2 - 11503163
AN - SCOPUS:0035451571
SN - 0148-7299
VL - 102
SP - 353
EP - 358
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 4
ER -