title: 22q13.2q13.32 genomic regions associated with severity of speech delay, developmental delay, and physical features in Phelan-McDermid syndrome.
abstract: OBJECTIVE
  Phelan-McDermid syndrome is a developmental disability syndrome with varying deletions of 22q13 and varying clinical severity. We tested the hypothesis that, in addition to loss of the telomeric gene SHANK3, specific genomic regions within 22q13 are associated with important clinical features.
  
  
  METHODS
  We used a customized oligo array comparative genomic hybridization of 22q12.3-terminus to obtain deletion breakpoints in a cohort of 70 patients with terminal 22q13 deletions. We used association and receiver operating characteristic statistical methods in a novel manner and also incorporated protein interaction networks to identify 22q13 genomic locations and genes associated with clinical features.
  
  
  RESULTS
  Specific genomic regions and candidate genes within 22q13.2q13.32 were associated with severity of speech/language delay, neonatal hypotonia, delayed age at walking, hair-pulling behaviors, male genital anomalies, dysplastic toenails, large/fleshy hands, macrocephaly, short and tall stature, facial asymmetry, and atypical reflexes. We also found regions suggestive of a negative association with autism spectrum disorders.
  
  
  CONCLUSIONS
  This work advances the field of research beyond the observation of a correlation between deletion size and phenotype and identifies candidate 22q13 loci, and in some cases specific genes, associated with singular clinical features observed in Phelan-McDermid syndrome. Our statistical approach may be useful in genotype-phenotype analyses for other microdeletion or microduplication syndromes.
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Sarasua
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Alka
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Boccuto
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Chen
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Sharp
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rollins
authors.affiliation: 1] Greenwood Genetic Center, Greenwood, South Carolina, USA [2] Deceased.
authors.forename: Julianne S
authors.initials: JS
authors.lastname: Collins
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Katy
authors.initials: K
authors.lastname: Phelan
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina, USA.
authors.forename: Barbara R
authors.initials: BR
authors.lastname: DuPont
mesh_terms: D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007805:Language Development Disorders / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human