title: Excess of runs of homozygosity is associated with severe cognitive impairment in intellectual disability.
abstract: OBJECTIVE
  The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees.
  
  
  METHODS
  We investigated (i) the runs of homozygosity distribution between syndromic and nonsyndromic ID (ii) the effect of runs of homozygosity on the ID degree, using the intelligence quotient score.
  
  
  RESULTS
  Our data revealed no significant differences in the first analysis; instead we detected significantly larger runs of homozygosity stretches in severe ID compared to nonsevere ID cases (P = 0.007), together with an increase of the percentage of genome covered by runs of homozygosity (P = 0.03).
  
  
  CONCLUSIONS
  In accord with the recent findings regarding autism and other neurological disorders, this study reveals the important role of autosomal recessive variants in intellectual disability. The amount of homozygosity seems to modulate the degree of cognitive impairment despite the intellectual disability cause.
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gandin
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Faletra
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Faletra
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
authors.forename: Vanna
authors.initials: V
authors.lastname: Pecile
authors.affiliation: Department of Pediatrics, University of Torino, Torino, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Ferrero
authors.affiliation: Department of Pediatrics, University of Torino, Torino, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Biamino
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Palumbo
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.affiliation: Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.affiliation: Unit of Pediatrics and Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Belcaro
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Vozzi
authors.affiliation: 1] Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy [2] Institute for Maternal and Child Health, IRCCS "Burlo Garofolo," Trieste, Italy.
authors.forename: Adamo P
authors.initials: AP
authors.lastname: d'Adamo
mesh_terms: D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype