title: Subtelomeric imbalances in phenotypically normal individuals.
abstract: Subtelomeric imbalances are identified in approximately 5% of patients with idiopathic mental retardation (MR) and multiple congenital anomalies (MCA). Because of this high incidence, screening for subtelomeric anomalies became part of the routine genetic evaluation of MCA/MR patients. In contrast to the general view that subtelomeric imbalances cause MCA/MR, we report here 15 subtelomeric copy-number changes in 12 families in which the imbalance is inherited from a phenotypically normal parent. We detected inherited deletions at subtelomeres 2q, 3p, 4p, 4q, 6q, 10q, 17p, 17q, Xp, and Yq and duplications at 1q, 4q, 10q, and 11q. Interestingly, in addition to small deletions (<1 Mb) also unexpected large deletions and duplications up to 7.8 Mb were detected. Taken together with previous reports, a total of 16 subtelomeric duplications and 18 deletions inherited from a phenotypically normal parent have now been reported. Clearly, more extensive genotype-phenotype correlations are needed to better understand the phenotypic consequences of these subtelomeric copy number variations and to resolve the current uncertainty for genetic counseling in postnatal and prenatal diagnosis.
authors.affiliation: Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Irina
authors.initials: I
authors.lastname: Balikova
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Bernard
authors.initials: B
authors.lastname: Thienpont
authors.forename: Montse
authors.initials: M
authors.lastname: Urbina
authors.forename: Martine
authors.initials: M
authors.lastname: Doco-Fenzy
authors.forename: Marjan
authors.initials: M
authors.lastname: de Rademaeker
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
authors.forename: Frank
authors.initials: F
authors.lastname: Kooy
authors.forename: Janneke
authors.initials: J
authors.lastname: van den Ende
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D016615:Telomere / Q000648:ultrastructure*