title: Narrowing of the responsible region for severe developmental delay and autistic behaviors in WAGR syndrome down to 1.6 Mb including PAX6, WT1, and PRRG4.
abstract: Interstitial deletions of the 11p13 region are known to cause WAGR (Wilms tumor, aniridia, genitourinary malformation, and "mental retardation") syndrome, a contiguous gene deletion syndrome due to haploinsufficiencies of the genes in this region, including WT1 and PAX6. Developmental delay and autistic features are major complications of this syndrome. Previously, some genes located in this region have been suggested as responsible for autistic features. In this study, we identified two patients who showed the chromosomal deletions involving 11p13. Patient 1, having an 8.6 Mb deletion of chr11p14.1p12:29,676,434-38,237,948, exhibited a phenotype typical of WAGR syndrome and had severe developmental delay and autistic behaviors. On the other hand, Patient 2 had a larger aberration region in 11p14.1-p12 which was split into two regions, that is, a 2.2-Mb region of chr11p14.1: 29,195,161-31,349,732 and a 10.5-Mb region of chr11p13p12: 32,990,627-43,492,580. As a consequence, 1.6 Mb region of the WAGR syndrome critical region was intact between the two deletions. This patient showed no symptom of WAGR syndrome and no autistic behaviors. Therefore, the region responsible for severe developmental delay and autistic features on WAGR syndrome can be narrowed down to the region remaining intact in Patient 2. Thus, the unique genotype identified in this study suggested that haploinsufficiencies of PAX6 or PRRG4 included in this region are candidate genes for severe developmental delay and autistic features characteristic of WAGR syndrome.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS), Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Masami
authors.initials: M
authors.lastname: Togawa
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.forename: Noriko
authors.initials: N
authors.lastname: Sangu
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D017624:WAGR Syndrome / Q000175:diagnosis* / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; C423615:PRRG4 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D025721:WT1 Proteins
keywords: PAX6; PRRG4; WAGR syndrome; WT1; autistic feature