title: "Familial" versus "sporadic" intellectual disability: contribution of subtelomeric rearrangements.
abstract: BACKGROUND
  Cryptic subtelomeric rearrangements have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been studied. As positive family history of ID had been proposed as an important and significant predicting factor of subtelomeric rearrangements, it was assumed that the contribution of subtelomeric aberrations in familial ID would be much more than the sporadic ones. Three hundred and twenty two patients from 102 unrelated families with more than two ID patients in the first degree relatives have been investigated. Assessment of subtelomeric rearrangements were carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique. Detected aberrations were then confirmed by Fluorescence in Situ Hybridization (FISH) method.
  
  
  RESULTS
  Among the families studied, 27.4% had 4-12, 36.3% had 3 and 36.3% had 2 affected individuals in the first degree relatives. One unbalanced translocation and 4 polymorphic changes were detected. The prevalence of clinically significant subtelomeric rearrangements was 0.98%.
  
  
  CONCLUSIONS
  This is the first investigation of subtelomeric aberrations in a large sample set of familial ID patients. Our results show that the contribution of subtelomeric rearrangements to familial ID is not as much as what had been determined for sporadic ones in the literature. Moreover, this study shows that the positive family history by alone, cannot be the most important and determining indicator of subtelomeric aberrations while it would be a good predicting factor when associated with dysmorphism or congenital malformations. These findings propose that other cryptic chromosomal abnormalities or even single gene disorders may be the main cause of familial ID rather than subtelomeric aberrations.
authors.affiliation: Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran. Saeed@ghaffari.org.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rafati
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ghadirzadeh
authors.forename: Yaser
authors.initials: Y
authors.lastname: Heshmati
authors.forename: Homeira
authors.initials: H
authors.lastname: Adibi
authors.forename: Zarrintaj
authors.initials: Z
authors.lastname: Keihanidoust
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Eshraghian
authors.forename: Jila
authors.initials: J
authors.lastname: Dastan
authors.forename: Azadeh
authors.initials: A
authors.lastname: Hoseini
authors.forename: Marzieh
authors.initials: M
authors.lastname: Purhoseini
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Ghaffari