Incomplete Penetrance, Partial Expressivity, or Benign Variant: Xp22.31, a Copy Number Variation Commonly Seen in Patients w/Intellectual Disability

2011

Array comparative genomic hybridization is a first-tier diagnostic test for persons with autism spectrum disorders, unexplained development delay, and unexplained intellectual disability. Xp22.31 is a relatively common area for copy number variation and has presented clinicians with the difficult task in counseling patients. The region has been implicated as a possible cause of X-linked mental retardation, autism, and a variety of physical manifestations. Deletions as well as duplications in the Xp22.31 region have been reported on array comparative genomic hybridization studies as pathogenic, benign variants, and aberrations of unknown clinical significance. The Xp22.31 region is home to several genes including: HDHD1A, STS, VCX, PNPLA4, hsa-mir-651, VCX2, VCX-C, KAL1, and FAM9A. Of the nine patients that fit our criteria with Xp22.31 genomic dosage changes, five have nonsyndromic autism and the other four have significant psychological diagnoses. We suggest that anomalies in the Xp22.31 region, including duplications, should not be designated as benign.

Conference presentations and posters presented

Professionals, Students

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