المستخلص
Autism spectrum disorder (ASD) is a heterogenous condition with a wide range of
elements contributing to its presentation, including both common and rare genetic
variants, as well as environmental and developmental factors. In rare instances, ASD
is associated with known syndromes such as tuberous sclerosis, 22q11 microdeletion
or Down syndrome. Over the past two decades, as a result of revolutionary
technology including Next Generation Sequencing (NGS) and Optical Genome
Mapping (OGM), autism genetics research grew rapidly leading to large number of
discoveries, including new genetic loci, hundreds of alterations in the genetic
sequence, expression, epigenetic transformation, and interactions with other
physiological and environmental systems have been found in association with ASD.
The present work is aimed to characterize a cohort of 100 pediatric patients aged
between 3 and 12 years, affected by non syndromic ASD according to the DSM-V. This
approach has allowed the identification of causative genetic variants in at least seven
families. The identified variants were harbored in well known genes involved in the
pathogenesis of Autism Spectrum Disorder and non-syndromic mental retardation,
such as TNIK and SHANK3. Potentially causative variants have also been identified in
susceptibility ASD genes, such as SHANK2 and NRXN3. Interestingly, rare de novo and
compoud heterozygous variants have also been identified in genes never described
before in association with ASD, but related to nervous system development,
mantainance and functional regulation. By using molecular modeling and dynamics
simulation techniques, we are investigating the impact of this variants on the protein
stability and interaction network, thereby providing a preliminary assessment of its
mechanistic role.
In conclusion, here we discuss the results obtained in this study and the recent
advances in the ASD genetics and genomics, to better understand role of of the ASD-
associated genetic factors. The future of genetic research, due to interdisciplinary
collaborations, could facilitate the personalized medicine as well as genetic
counselling and early intervention strategies
elements contributing to its presentation, including both common and rare genetic
variants, as well as environmental and developmental factors. In rare instances, ASD
is associated with known syndromes such as tuberous sclerosis, 22q11 microdeletion
or Down syndrome. Over the past two decades, as a result of revolutionary
technology including Next Generation Sequencing (NGS) and Optical Genome
Mapping (OGM), autism genetics research grew rapidly leading to large number of
discoveries, including new genetic loci, hundreds of alterations in the genetic
sequence, expression, epigenetic transformation, and interactions with other
physiological and environmental systems have been found in association with ASD.
The present work is aimed to characterize a cohort of 100 pediatric patients aged
between 3 and 12 years, affected by non syndromic ASD according to the DSM-V. This
approach has allowed the identification of causative genetic variants in at least seven
families. The identified variants were harbored in well known genes involved in the
pathogenesis of Autism Spectrum Disorder and non-syndromic mental retardation,
such as TNIK and SHANK3. Potentially causative variants have also been identified in
susceptibility ASD genes, such as SHANK2 and NRXN3. Interestingly, rare de novo and
compoud heterozygous variants have also been identified in genes never described
before in association with ASD, but related to nervous system development,
mantainance and functional regulation. By using molecular modeling and dynamics
simulation techniques, we are investigating the impact of this variants on the protein
stability and interaction network, thereby providing a preliminary assessment of its
mechanistic role.
In conclusion, here we discuss the results obtained in this study and the recent
advances in the ASD genetics and genomics, to better understand role of of the ASD-
associated genetic factors. The future of genetic research, due to interdisciplinary
collaborations, could facilitate the personalized medicine as well as genetic
counselling and early intervention strategies
الكلمات المفتاحية
Autism spectrum disorder (ASD)
techniques
strategies
heterogenous
