title: Additional chromosomal abnormalities in patients with a previously detected abnormal karyotype, mental retardation, and dysmorphic features.
abstract: The detection of chromosomal abnormalities in patients with mental retardation (MR) and dysmorphic features increases with improvements of molecular cytogenetic methods. We report on six patients referred for detailed characterization of chromosomal abnormalities (four translocations, one inversion, one deletion) detected by conventional cytogenetics, in whom metaphase CGH revealed imbalances not involved in the initially detected rearrangements. The detected abnormalities were validated by real-time PCR. Parents were investigated by CGH in four cases. The genomic screening revealed interstitial deletions of 2q33.2-q34, 3p21, 4q12-q13.1, 6q25, 13q22.2-q31.1, and 14q12. The estimated minimum sizes of the deletions ranged from 2.65 to 9.27 Mb. The CGH assay did not reveal imbalances that colocalized with the breakpoints of the inversion or the translocations. The deletion of 6q included ESR1, in which polymorphisms are associated with variation of adult height. FOXG1B, known to be involved in cortical development, was located in the 14q deletion. The results illustrate that whole-genome molecular cytogenetic analysis of phenotypically affected patients with abnormal conventional karyotypes may detect inapparent molecular cytogenetic abnormalities in patients with microscopic chromosomal abnormalities and that these data provide additional information of clinical importance.
authors.affiliation: Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark. anne-marie.bisgaard.pedersen@rh.hosp.dk
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bisgaard
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.forename: Birgit
authors.initials: B
authors.lastname: Jepsen
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.forename: Monika
authors.initials: M
authors.lastname: Cohen
authors.forename: Bente
authors.initials: B
authors.lastname: Hamborg-Petersen
authors.forename: Thue
authors.initials: T
authors.lastname: Bryndorf
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Flemming
authors.initials: F
authors.lastname: Skovby
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male