TY - JOUR
T1 - Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome
AU - Schlaubitz, Silke
AU - Yatsenko, Svetlana A.
AU - Smith, Laurie D.
AU - Keller, Kory L.
AU - Vissers, Lisenka E.
AU - Scott, Daryl A.
AU - Wei, Wen Cai
AU - Reardon, William
AU - Abdul-Rahman, Omar A.
AU - Lammer, Edward J.
AU - Lifchez, Caroline A.
AU - Magenis, Ellen
AU - Veltman, Joris A.
AU - Stankiewicz, Pawel
AU - Zabel, Bernhard U.
AU - Lee, Brendan
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - We describe our findings in a 46,XY female with a clinical features of Genitopatellar syndrome (GPS) and confirmed hermaphroditism with ovotestes, and five additional patients with GPS. GPS is a genetic disorder characterized by renal and genital anomalies, joint dislocation, aplastic or hypoplastic and often displaced patellae, minor facial anomalies, and mental retardation. The genital anomalies clearly distinguish GPS from nail-patella syndrome (NPS) that has similar features, but additionally shows hypoplastic finger-and toenails as found in the 46,XY female. In our patients no mutation was found in the coding regions of WNT4, WNT7A, TBX4, and LMX1B. Fluorescent in situ hybridization (FISH) and array-based comparative genome hybridization (aCGH) analysis showed a 3 Mb deletion of LMX1B, NR6A1, and NR5A1 (SF1) in the 46,XY female. This is the first report of a microdeletion causing haploinsuffiency of LMX1B and NR5A1. The deletion of LMX1B is responsible for the knee anomalies and the deletion of NR5A1 likely causes the sex reversal. Cytogenetic analysis of the five additional patients with diagnosed GPS failed to identify a similar microdeletion, or inversion of a potentially regulatory element between the two genes. This suggests that the locus 9q33-9q34 can be excluded for GPS and that the presented case is unique in its combination of GPS and NPS features caused by a microdeletion associated with loss of function of LMX1B and NR5A1.
AB - We describe our findings in a 46,XY female with a clinical features of Genitopatellar syndrome (GPS) and confirmed hermaphroditism with ovotestes, and five additional patients with GPS. GPS is a genetic disorder characterized by renal and genital anomalies, joint dislocation, aplastic or hypoplastic and often displaced patellae, minor facial anomalies, and mental retardation. The genital anomalies clearly distinguish GPS from nail-patella syndrome (NPS) that has similar features, but additionally shows hypoplastic finger-and toenails as found in the 46,XY female. In our patients no mutation was found in the coding regions of WNT4, WNT7A, TBX4, and LMX1B. Fluorescent in situ hybridization (FISH) and array-based comparative genome hybridization (aCGH) analysis showed a 3 Mb deletion of LMX1B, NR6A1, and NR5A1 (SF1) in the 46,XY female. This is the first report of a microdeletion causing haploinsuffiency of LMX1B and NR5A1. The deletion of LMX1B is responsible for the knee anomalies and the deletion of NR5A1 likely causes the sex reversal. Cytogenetic analysis of the five additional patients with diagnosed GPS failed to identify a similar microdeletion, or inversion of a potentially regulatory element between the two genes. This suggests that the locus 9q33-9q34 can be excluded for GPS and that the presented case is unique in its combination of GPS and NPS features caused by a microdeletion associated with loss of function of LMX1B and NR5A1.
KW - Genitopatellar syndrome features
KW - LMX1B
KW - NR5A1
KW - Ovotestes
KW - Sex reversal
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U2 - 10.1002/ajmg.a.31685
DO - 10.1002/ajmg.a.31685
M3 - Article
C2 - 17431898
AN - SCOPUS:34248186062
SN - 1552-4825
VL - 143
SP - 1071
EP - 1081
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 10
ER -