title: Further clinical and molecular delineation of the 15q24 microdeletion syndrome.
abstract: BACKGROUND
  Chromosome 15q24 microdeletion syndrome is a rare genomic disorder characterised by intellectual disability, growth retardation, unusual facial morphology and other anomalies. To date, 20 patients have been reported; 18 have had detailed breakpoint analysis.
  
  
  OBJECTIVE
  To further delineate the features of the 15q24 microdeletion syndrome, the clinical and molecular characterisation of fifteen patients with deletions in the 15q24 region was performed, nearly doubling the number of reported patients.
  
  
  METHODS
  Breakpoints were characterised using a custom, high-density array comparative hybridisation platform, and detailed phenotype information was collected for each patient.
  
  
  RESULTS
  Nine distinct deletions with different breakpoints ranging in size from 266 kb to 3.75 Mb were identified. The majority of breakpoints lie within segmental duplication (SD) blocks. Low sequence identity and large intervals of unique sequence between SD blocks likely contribute to the rarity of 15q24 deletions, which occur 8-10 times less frequently than 1q21 or 15q13 microdeletions in our series. Two small, atypical deletions were identified within the region that help delineate the critical region for the core phenotype in the 15q24 microdeletion syndrome.
  
  
  CONCLUSIONS
  The molecular characterisation of these patients suggests that the core cognitive features of the 15q24 microdeletion syndrome, including developmental delays and severe speech problems, are largely due to deletion of genes in a 1.1-Mb critical region. However, genes just distal to the critical region also play an important role in cognition and in the development of characteristic facial features associated with 15q24 deletions. Clearly, deletions in the 15q24 region are variable in size and extent. Knowledge of the breakpoints and size of deletion combined with the natural history and medical problems of our patients provide insights that will inform management guidelines. Based on common phenotypic features, all patients with 15q24 microdeletions should receive a thorough neurodevelopmental evaluation, physical, occupational and speech therapies, and regular audiologic and ophthalmologic screening.
authors.affiliation: Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, DC 98195, USA. hmefford@u.washington.edu
authors.forename: Heather C
authors.initials: HC
authors.lastname: Mefford
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: Natasha
authors.initials: N
authors.lastname: Shur
authors.forename: Anne M
authors.initials: AM
authors.lastname: Slavotinek
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Cox
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Helen V
authors.initials: HV
authors.lastname: Firth
authors.forename: Lionel
authors.initials: L
authors.lastname: Willatt
authors.forename: Patricia
authors.initials: P
authors.lastname: Wheeler
authors.forename: Eric M
authors.initials: EM
authors.lastname: Morrow
authors.forename: Joseph
authors.initials: J
authors.lastname: Cook
authors.forename: Rachel
authors.initials: R
authors.lastname: Sullivan
authors.forename: Albert
authors.initials: A
authors.lastname: Oh
authors.forename: Marie T
authors.initials: MT
authors.lastname: McDonald
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zonana
authors.forename: Kory
authors.initials: K
authors.lastname: Keller
authors.forename: Mark C
authors.initials: MC
authors.lastname: Hannibal
authors.forename: Susie
authors.initials: S
authors.lastname: Ball
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kussmann
authors.forename: Jerome
authors.initials: J
authors.lastname: Gorski
authors.forename: Susan
authors.initials: S
authors.lastname: Zelewski
authors.forename: Valerie
authors.initials: V
authors.lastname: Banks
authors.forename: Wendy
authors.initials: W
authors.lastname: Smith
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Smith
authors.forename: Lindsay
authors.initials: L
authors.lastname: Paull
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Rosenbaum
authors.forename: David J
authors.initials: DJ
authors.lastname: Amor
authors.forename: Joao
authors.initials: J
authors.lastname: Silva
authors.forename: Allen
authors.initials: A
authors.lastname: Lamb
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D056916:Segmental Duplications, Genomic; D013577:Syndrome