P792: Conflicting genotype-phenotype data on ITSN1 as a candidate gene for neurodevelopmental disorders

Introduction: The majority of 22q11.2microdeletion syndrome cases are de novo with 5-10% of cases being inherited.22q11.2microduplication syndrome is diagnosed less often but is almost always inherited from an asymptomatic or mildly symptomatic parent.Here we report an individual identified with 22q11.2microdeletion syndrome with a strong family history of 22q11.2microduplication syndrome and describe inheritance of the deletion from his mother who was determined to be a balanced heterozygote of both rearrangements.Case Presentation: A 7 month old boy presented to genetics with mild developmental delay, a small patent foramen ovale, subtle dysmorphic features and a strong family history of 22q11.2microduplication syndrome.Both of his maternal cousins were diagnosed 22q11.2microduplication syndrome with congenital anomalies requiring surgical repair.Diagnostic Workup: CGH microarray was performed on peripheral blood from the patient and identified the common 2.54 Mb deletion at chromosome band 22q11.2spanning breakpoints A through D. Subsequent microarray testing of the patient's mother revealed a normal, two copy state for the 22q11.2region.Of note, two sisters of the mother were previously tested by CGH microarray and found to carry the 22q11.2microduplication.FISH testing with the HIRA probe revealed that the mother carried two copies of the locus by interphase FISH analysis but only one signal was visible by metaphase FISH.These results suggested that that one chromosome 22 homologue harbored the 22q11.2microduplication, and the other homologue was deleted for the 22q11.2region.