title: Comparison of two subtelomeric assays for the screening of chromosomal rearrangements: analysis of 383 patients, literature review and further recommendations.
abstract: Intellectual disability (ID) and global development delay (GDD) are caused by genetic factors such as subtelomeric rearrangements (SR) in 25 % of patients. There are several assays currently available to detect SR, but subtelomeric fluorescence in situ hybridisation (Subt-FISH) and subtelomeric multiplex ligation-dependent probe amplification (Subt-MLPA) have been the most frequently used. However, the diagnostic yield of each technique has not been compared. We reviewed the results of SR screening over a ten-year period in Chilean patients with ID/GDD using Subt-FISH and/or Subt-MLPA, compared the diagnostic yield of both tools and reviewed the corresponding literature. A total of 383 cases were included in this study, of which 53.8 % were males. The overall diagnostic yield was 8.9 % between both methods, but Subt-MLPA showed a higher performance than Subt-FISH (p = 0.002). A total of 4,181 patients with ID/GDD have been studied worldwide with Subt-MLPA and other subtelomeric assays, and 244 (5.84 %) had a pathogenic SR. It is estimated that Subt-MLPA may detect 92.6 % of the total cases with SR. The capacity of detecting tandem duplication and other critical regions, as well as the use of two MLPA kits, may explain the higher performance of this tool over Subt-FISH. Therefore, we recommend the use of this subtelomeric method as a cost-effective way to study ID/GDD patients.
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Lorena
authors.initials: L
authors.lastname: Santa María
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile. vfaundes@inta.cl.
authors.forename: Víctor
authors.initials: V
authors.lastname: Faundes
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Bianca
authors.initials: B
authors.lastname: Curotto
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Morales
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.|Escuela de Tecnología Médica, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
authors.forename: Karla
authors.initials: K
authors.lastname: Morales
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Solange
authors.initials: S
authors.lastname: Aliaga
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Pugin
authors.affiliation: Laboratorio de Genética y Enfermedades Metabólicas, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Av. El Líbano 5524, Macul, Casilla 138-11, Santiago, Chile.
authors.forename: María Angélica
authors.initials: MA
authors.lastname: Alliende
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002677:Chile; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D060885:Multiplex Polymerase Chain Reaction
keywords: Fluorescence in situ hybridisation; Global development delay; Intellectual disability; Multiplex ligation-dependent probe amplification; Subtelomeric rearrangements