Ilaria Gandin1, Flavio Faletra2, Francesca Faletra2, Massimo Carella3, Vanna Pecile2, Giovanni B Ferrero4, Elisa Biamino4, Pietro Palumbo3, Orazio Palumbo3, Paolo Bosco5, Corrado Romano6, Chiara Belcaro1, Diego Vozzi2, Adamo P d'Adamo7. 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. 3. Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. 4. Department of Pediatrics, University of Torino, Torino, Italy. 5. Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy. 6. Unit of Pediatrics and Medical Genetics, IRCCS Associazione Oasi Maria Santissima, Troina, Italy. 7. 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.
Abstract
PURPOSE: 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). CONCLUSION: 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.
PURPOSE: 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). CONCLUSION: 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.
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