Genotype-phenotype mapping of chromosome 18q deletions by high-resolution array CGH: an update of the phenotypic map

Am J Med Genet A. 2007 Aug 15;143A(16):1858-67. doi: 10.1002/ajmg.a.31850.


Partial deletions of the long arm of chromosome 18 lead to variable phenotypes. Common clinical features include a characteristic face, short stature, congenital aural atresia (CAA), abnormalities of the feet, and mental retardation (MR). The presence or absence of these clinical features may depend on the size and position of the deleted region. Conversely, it is also known that patients whose breakpoints are localized within the same chromosome band may exhibit distinct phenotypes. New molecular techniques such as array CGH allow for a more precise determination of breakpoints in cytogenetic syndromes, thus leading to better-defined genotype-phenotype correlations. In order to update the phenotypic map for chromosome 18q deletions, we applied a tiling resolution chromosome 18 array to determine the exact breakpoints in 29 patients with such deletions. Subsequently, we linked the genotype to the patient's phenotype and integrated our results with those previously published. Using this approach, we were able to refine the critical regions for microcephaly (18q21.33), short stature (18q12.1-q12.3, 18q21.1-q21.33, and 18q22.3-q23), white matter disorders and delayed myelination (18q22.3-q23), growth hormone insufficiency (18q22.3-q23), and CAA (18q22.3). Additionally, the overall level of MR appeared to be mild in patients with deletions distal to 18q21.33 and severe in patients with deletions proximal to 18q21.31. The critical region for the 'typical' 18q-phenotype is a region of 4.3 Mb located within 18q22.3-q23. Molecular characterization of more patients will ultimately lead to a further delineation of the critical regions and thus to the identification of candidate genes for these specific traits.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Chromosome Aberrations
  • Chromosome Deletion*
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 18*
  • DNA Mutational Analysis
  • Genotype
  • Humans
  • Karyotyping
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis / methods*
  • Phenotype
  • Syndrome