title: Genome-wide screening using automated fluorescent genotyping to detect cryptic cytogenetic abnormalities in children with idiopathic syndromic mental retardation.
abstract: Mental retardation (MR) is the most common developmental disability, affecting approximately 2% of the population. The causes of MR are diverse and poorly understood, but chromosomal rearrangements account for 4-28% of cases, and duplications/deletions smaller than 5 Mb are known to cause syndromic MR. We have previously developed a strategy based on automated fluorescent microsatellite genotyping to test for telomere integrity. This strategy detected about 10% of cryptic subtelomeric rearrangements in patients with idiopathic syndromic MR. Because telomere screening is a first step toward the goal of analyzing the entire genome for chromosomal rearrangements in MR, we have extended our strategy to 400 markers evenly distributed along the chromosomes to detect interstitial anomalies. Among 97 individuals tested, three anomalies were found: two deletions (one in three siblings) and one parental disomy. These results emphasize the value of a genome-wide microsatellite scan for the detection of interstitial aberrations and demonstrate that automated genotyping is a sensitive method that not only detects small interstitial rearrangements and their parental origin but also provides a unique opportunity to detect uniparental disomies. This study will hopefully contribute to the delineation of new contiguous gene syndromes and the identification of new imprinted regions.
authors.affiliation: INSERM U393 et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Borck
authors.forename: M
authors.initials: M
authors.lastname: Rio
authors.forename: D
authors.initials: D
authors.lastname: Sanlaville
authors.forename: R
authors.initials: R
authors.lastname: Redon
authors.forename: F
authors.initials: F
authors.lastname: Molinari
authors.forename: D
authors.initials: D
authors.lastname: Bacq
authors.forename: O
authors.initials: O
authors.lastname: Raoul
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: M
authors.initials: M
authors.lastname: Le Merrer
authors.forename: M-C
authors.initials: MC
authors.lastname: de Blois
authors.forename: M
authors.initials: M
authors.lastname: Prieur
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: N P
authors.initials: NP
authors.lastname: Carter
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: L
authors.initials: L
authors.lastname: Colleaux
mesh_terms: D002648:Child; D002869:Chromosome Aberrations; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008856:Microscopy, Fluorescence; D009693:Nucleic Acid Hybridization; D016615:Telomere / Q000235:genetics