title: Multiplex ligation-dependent probe amplification to detect subtelomeric rearrangements in routine diagnostics.
abstract: Subtelomeric rearrangements are believed to be responsible for 5-7% of idiopathic mental retardation cases. Due to the relative complexity and high cost of the screening methods used till now, only preselected patient populations including mostly the more severely affected cases have been screened. Recently, multiplex ligation-dependent probe amplification (MLPA) has been adapted for use in subtelomeric screening, and we have incorporated this technique into routine diagnostics of our laboratory. Since the evaluation of MLPA as a screening method, we tested 275 unselected patients with idiopathic mental retardation and detected 12 possible subtelomeric aberrations: a der(11)t(11;20)(qter;qter), a 19pter duplication, a der(18)t(18;10)(qter; pter), a 15qter deletion, a 8pter deletion, a 6qter deletion, a der(X)t(X;1)(pter;qter), a der(X)t(X;3)(pter;pter), a 5qter duplication, a 3pter deletion, and two 3qter duplications. The patients can be subdivided into two groups: the first containing de novo rearrangements that are likely related to the clinical presentation of the patient and the second including aberrations also present in one of the parents that may or may not be causative of the mental retardation. In our patient cohort, five (1.8%) subtelomeric rearrangements were de novo, three (1.1%) rearrangements were familial and suggestively disease causing, and four (1.5%) were possible polymorphisms. This high frequency of subtelomeric abnormalities detected in an unselected population warrants further investigation about the feasibility of routine screening for subtelomeric aberrations in mentally retarded patients.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp and University Hospital Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Rooms
authors.forename: E
authors.initials: E
authors.lastname: Reyniers
authors.forename: W
authors.initials: W
authors.lastname: Wuyts
authors.forename: K
authors.initials: K
authors.lastname: Storm
authors.forename: R
authors.initials: R
authors.lastname: van Luijk
authors.forename: S
authors.initials: S
authors.lastname: Scheers
authors.forename: J
authors.initials: J
authors.lastname: Wauters
authors.forename: J
authors.initials: J
authors.lastname: van den Ende
authors.forename: M
authors.initials: M
authors.lastname: Biervliet
authors.forename: F
authors.initials: F
authors.lastname: Eyskens
authors.forename: G
authors.initials: G
authors.lastname: van Goethem
authors.forename: A
authors.initials: A
authors.lastname: Laridon
authors.forename: B
authors.initials: B
authors.lastname: Ceulemans
authors.forename: W
authors.initials: W
authors.lastname: Courtens
authors.forename: R F
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015342:DNA Probes; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D022521:Ligase Chain Reaction / Q000379:methods*; D008297:Male; D008969:Molecular Sequence Data; D016615:Telomere
chemical_list: D015342:DNA Probes