title: 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.
abstract: 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.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Silke
authors: S
authors: Schlaubitz
authors: Svetlana A
authors: SA
authors: Yatsenko
authors: Laurie D
authors: LD
authors: Smith
authors: Kory L
authors: KL
authors: Keller
authors: Lisenka E
authors: LE
authors: Vissers
authors: Daryl A
authors: DA
authors: Scott
authors: Wei Wen
authors: WW
authors: Cai
authors: William
authors: W
authors: Reardon
authors: Omar A
authors: OA
authors: Abdul-Rahman
authors: Edward J
authors: EJ
authors: Lammer
authors: Caroline A
authors: CA
authors: Lifchez
authors: Ellen
authors: E
authors: Magenis
authors: Joris A
authors: JA
authors: Veltman
authors: Pawel
authors: P
authors: Stankiewicz
authors: Bernhard U
authors: BU
authors: Zabel
authors: Brendan
authors: B
authors: Lee
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D004252:DNA Mutational Analysis; D012734:Disorders of Sex Development; D005260:Female; D006066:Gonads / Q000002:abnormalities*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D060850:LIM-Homeodomain Proteins; D008297:Male; D010329:Patella / Q000002:abnormalities*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D054339:Steroidogenic Factor 1; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors