title: A familial pericentric inversion of chromosome 11 associated with a microdeletion of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or eye anomalies.
abstract: Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L, and ELP4 are previously reported to have downstream transcriptional effects on the expression of PAX6, due to a downstream regulatory region (DRR). Currently, no clear genotype-phenotype correlations have been established allowing for conclusive information regarding the exact location of the PAX6 DRR, though its location has been approximated in mouse models to be within the Elp4 gene. Of the clinical reports currently published examining patients with intact PAX6 genes but harboring deletions identified in genes downstream of PAX6, 100% indicate phenotypes which include aniridia, whereas approximately half report additional eye deformities, autism, or intellectual disability. In this clinical report, we present a 12-year-old male patient, his brother, and mother with pericentric inversions of chromosome 11 associated with submicroscopic interstitial deletions of 11p13 and duplications of 11q22.3. The inversions were identified by standard cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The patient's phenotype includes intellectual disability, speech abnormalities, and autistic behaviors, but interestingly neither the patient, his brother, nor mother have aniridia or other eye anomalies. To the best of our knowledge, these findings in three family members represent the only reported cases with 11p13 deletions downstream of PAX6 not demonstrating phenotypic characteristics of aniridia or abnormal eye development. Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6.
authors.affiliation: Center for Genetic Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lara
authors.initials: L
authors.lastname: Balay
authors.affiliation: Advocate Medical Group Genetics, Park Ridge, Illinois.
authors.forename: Ellen
authors.initials: E
authors.lastname: Totten
authors.affiliation: St. Alexius Medical Center, Hoffman Estates, Illinois.
authors.forename: Luna
authors.initials: L
authors.lastname: Okada
authors.affiliation: Advocate Children's Hospital, Oak Lawn, Illinois.
authors.forename: Sidney
authors.initials: S
authors.lastname: Zell
authors.affiliation: Advocate Children's Hospital, Oak Lawn, Illinois.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ticho
authors.affiliation: Advocate Children's Hospital, Oak Lawn, Illinois.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Israel
authors.affiliation: Advocate Medical Group Genetics, Park Ridge, Illinois.|Department of Cytogenetics, ACL Laboratories, Rosemont, Illinois.
authors.forename: Jillene
authors.initials: J
authors.lastname: Kogan
mesh_terms: D015783:Aniridia / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D007446:Chromosome Inversion / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D020440:Gene Duplication / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D013064:Speech Disorders / Q000235:genetics
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins
keywords: 11p13 deletion; 11q22.3 duplication; PAX6; PAX6 downstream regulatory region; aniridia