PubMed1990
This annotation has been confined to well-established clinical syndromes with recently discovered chromosomal etiologies. It deliberately omits retinoblastoma, the oft-cited paradigm of a contiguous gene syndrome, since it is usually inherited as a Mendelian single gene disorder. However, it was recognition of both the deletion of band q14 of chromosome 13 in mentally retarded children with retinoblastoma, and the linkage of retinoblastoma with the genetic marker esterase D, which resulted in the eventual cloning of the gene. Also omitted are microdeletions of the X chromosome. These disorders are seen primarily in males, who manifest the phenotypic effects of the deletion of the loci of various combinations of adjacent genes: Duchenne muscular dystrophy, glycerol kinase deficiency, adrenal hypoplasia, optic albinism, hypogonadotropic hypogonadism and anosmia (Kallman syndrome), chondrodysplasia punctata and ichthyosis. Many are also mentally retarded. The third group omitted are Mendelian disorders occurring with atypical mental retardation (not usually part of the disorder), the presumption being that they include small deletions. It is expected that other contiguous gene syndromes will be recognized eventually; Rubinstein-Taybi and Cornelia de Lange syndromes are prime candidates. Why do deletions have such dramatic consequences when a normal homologue of the region is present? If their effects were due to the uncovering of recessive genes, we would expect to see greater variations in phenotype among carriers, including normal individuals whose deletions were masked by the protective effects of dominant alleles in the homologous regions. Imprinting--the 'stamping' of a gene as it passes through the germ line--provides a more satisfactory explanation.(ABSTRACT TRUNCATED AT 250 WORDS)