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.
Subject(s)
Abnormalities, Multiple/genetics , Chromosome Deletion , Chromosomes, Human, Pair 9 , Disorders of Sex Development , Gonads/abnormalities , Homeodomain Proteins/genetics , Patella/abnormalities , Receptors, Cytoplasmic and Nuclear/genetics , Transcription Factors/genetics , Child , Child, Preschool , Chromosome Banding , DNA Mutational Analysis , Female , Humans , Infant , LIM-Homeodomain Proteins , Male , Steroidogenic Factor 1 , SyndromeABSTRACT
Genitopatellar syndrome is a recently described disorder with characteristic facies, genital anomalies, absent patella, flexion contractures, microcephaly, renal anomalies, and mental retardation. The presence of affected siblings in two of the original families suggests autosomal recessive inheritance. We report a new patient that exhibits all of these cardinal features and is also the second case to have additional, more severe findings including a congenital heart defect, anal anomalies, and features of an ectodermal dysplasia, thus expanding the phenotype to include these manifestations.
