title: Genotype-phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21.
abstract: Down syndrome (DS) is one of the most frequent congenital birth defects, and the most common genetic cause of mental retardation. In most cases, DS results from the presence of an extra copy of chromosome 21. DS has a complex phenotype, and a major goal of DS research is to identify genotype-phenotype correlations. Cases of partial trisomy 21 and other HSA21 rearrangements associated with DS features could identify genomic regions associated with specific phenotypes. We have developed a BAC array spanning HSA21q and used array comparative genome hybridization (aCGH) to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA21. We report the identification and mapping of 30 pathogenic chromosomal aberrations of HSA21 consisting of 19 partial trisomies and 11 partial monosomies for different segments of HSA21. The breakpoints have been mapped to within approximately 85 kb. The majority of the breakpoints (26 of 30) for the partial aneuploidies map within a 10-Mb region. Our data argue against a single DS critical region. We identify susceptibility regions for 25 phenotypes for DS and 27 regions for monosomy 21. However, most of these regions are still broad, and more cases are needed to narrow down the phenotypic maps to a reasonable number of candidate genomic elements per phenotype.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. Robert.Lyle@medisin.uio.no
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Frédérique
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authors.lastname: Béna
authors.forename: Sarantis
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authors.lastname: Gagos
authors.forename: Corinne
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authors.lastname: Doco-Fenzy
authors.forename: Pascale
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authors.lastname: Cornillet-Lefèbvre
authors.forename: Anna
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authors.lastname: Pelet
authors.forename: Stanislas
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authors.forename: Nobuaki
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authors.lastname: Wakamatsu
authors.forename: Maria
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authors.lastname: Descartes
authors.forename: Judy C
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authors.lastname: Franklin
authors.forename: Lina
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authors.lastname: Florentin-Arar
authors.forename: Sophia
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authors.lastname: Kitsiou
authors.forename: Emilie
authors.initials: E
authors.lastname: Aït Yahya-Graison
authors.forename: Maher
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authors.lastname: Costantine
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Sinet
authors.forename: Jean M
authors.initials: JM
authors.lastname: Delabar
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D002872:Chromosome Deletion; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004314:Down Syndrome / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010641:Phenotype; D014314:Trisomy / Q000235:genetics*