Array-based comparative genomic hybridization identifies a high frequency of copy number variations in patients with syndromic overgrowth.
Overgrowth syndromes are a heterogeneous group of conditions including endocrine hormone disorders, several genetic syndromes and other disorders with unknown etiopathogenesis. Among genetic causes, chromosomal deletions and duplications such as dup(4)(p16.3), dup(15)(q26qter), del(9)(q22.32q22.33), del(22)(q13) and del(5)(q35) have been identified in patients with overgrowth. Most of them, however, remain undetectable using banding karyotype analysis. In this study, we report on the analysis using a 1-Mb resolution array-based comparative genomic hybridization (CGH) of 93 patients with either a recognizable overgrowth condition (ie, Sotos syndrome or Weaver syndrome) or an unclassified overgrowth syndrome. Five clinically relevant imbalances (three duplications and two deletions) were identified and the pathogenicity of two additional anomalies (one duplication and one deletion) is discussed. Altered segments ranged in size from 0.32 to 18.2 Mb, and no recurrent abnormality was identified. These results show that array-CGH provides a high diagnostic yield in patients with overgrowth syndromes and point to novel chromosomal regions associated with these conditions. Although chromosomal deletions are usually associated with growth retardation, we found that the majority of the imbalances detected in our patients are duplications. Besides their importance for diagnosis and genetic counseling, our results may allow to delineate new contiguous gene syndromes associated with overgrowth, pointing to new genes, the deregulation of which may be responsible for growth defect.
Departement de Génétique et INSERM U781, Université Paris Descartes, Hôpital Necker Enfants-Malades, Paris, France. valerie.malan@nck.aphp.fr
Valérie
V
Malan
Suzanne
S
Chevallier
Gwendoline
G
Soler
Christine
C
Coubes
Didier
D
Lacombe
Laurent
L
Pasquier
Jean
J
Soulier
Nicole
N
Morichon-Delvallez
Catherine
C
Turleau
Arnold
A
Munnich
Serge
S
Romana
Michel
M
Vekemans
Valérie
V
Cormier-Daire
Laurence
L
Colleaux
D000365:Age Determination by Skeleton; D002869:Chromosome Aberrations / Q000145:classification; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization / Q000379:methods*; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D014644:Genetic Variation; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D017384:Sequence Deletion