CONTEMPORARY APPROACH TO DIAGNOSIS OF GENETIC CAUSES OF INTELLECTUAL DISABILITY

Intellectual disability can follow any of the biological, environmental, and psychological events that are capable of producing a decline of cognitive functions. Some factors do not directly or inevitably cause intellectual disability but add to the effects of a previous primary cause. Genetic causes may be hereditary or non-hereditary, and may or may not produce specific syndromes. Some lead to inborn errors of metabolism. Causation, how to assess cause, and why knowledge of causation is important is covered in detail, followed by primary, secondary, and tertiary prevention, ethical problems of prevention, and the important of taking preventive aspects into account in all general and specific legislation, in operating procedures, and professional practice.

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Genetic causes of intellectual disability in a birth cohort: A population‐based study

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.37011 ◽

2015 ◽

Vol 167 (6) ◽

pp. 1204-1214 ◽

Cited By ~ 12

Author(s):

Simone M. Karam ◽

Mariluce Riegel ◽

Sandra L. Segal ◽

Têmis M. Félix ◽

Aluísio J. D. Barros ◽

...

Keyword(s):

Intellectual Disability ◽

Birth Cohort ◽

Population Based ◽

Population Based Study ◽

Genetic Causes

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Identification of genetic causes of congenital neurodevelopmental disorders using genome wide molecular technologies

Acta medica Lituanica ◽

10.6001/actamedica.v23i2.3324 ◽

2016 ◽

Vol 23 (2) ◽

pp. 73-85

Author(s):

Eglė Preikšaitienė ◽

Laima Ambrozaitytė ◽

Živilė Maldžienė ◽

Aušra Morkūnienė ◽

Loreta Cimbalistienė ◽

...

Keyword(s):

Intellectual Disability ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Single Gene ◽

Genetic Alterations ◽

Sequence Variants ◽

Candidate Sequence ◽

Genetic Causes ◽

Genome Wide ◽

Whole Exome

Background. Intellectual disability affects about 1–2% of the general population worldwide, and this is the leading socio-economic problem of health care. The evaluation of the genetic causes of intellectual disability is challenging because these conditions are genetically heterogeneous with many different genetic alterations resulting in clinically indistinguishable phenotypes. Genome wide molecular technologies are effective in a research setting for establishing the new genetic basis of a disease. We describe the first Lithuanian experience in genome-wide CNV detection and whole exome sequencing, presenting the results obtained in the research project UNIGENE.Materials and methods. The patients with developmental delay/intellectual disability have been investigated (n = 66). Diagnostic screening was performed using array-CGH technology. FISH and real time-PCR were used for the confirmation of gene-dose imbalances and investigation of parental samples. Whole exome sequencing using the next generation high throughput NGS technique was used to sequence the samples of 12 selected families.Results. 14 out of 66 patients had pathogenic copy number variants, and one patient had novel likely pathogenic aberration (microdeletion at 4p15.2). Twelve families have been processed for whole exome sequencing. Two identified sequence variants could be classified as pathogenic (in MECP2, CREBBP genes). The other families had several candidate intellectual disability gene variants that are of unclear clinical significance and must be further investigated for possible effect on the molecular pathways of intellectual disability.Conclusions. The genetic heterogeneity of intellectual disability requires genome wide approaches, including detection of chromosomal aberrations by chromosomal microarrays and whole exome sequencing capable of uncovering single gene mutations. This study demonstrates the benefits and challenges that accompany the use of genome wide molecular technologies and provides genotype-phenotype information on 32 patients with chromosomal imbalances and ID candidate sequence variants.

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Genetic Causes of Intellectual Disability: The Genes Controlling Cortical Development

Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability ◽

10.1016/b978-0-12-800109-7.00004-2 ◽

2016 ◽

pp. 43-64

Author(s):

Yoann Saillour ◽

Jamel Chelly

Keyword(s):

Intellectual Disability ◽

Cortical Development ◽

Genetic Causes

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Value for Money? Array Genomic Hybridization for Diagnostic Testing for Genetic Causes of Intellectual Disability

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2010.03.009 ◽

2010 ◽

Vol 86 (5) ◽

pp. 765-772 ◽

Cited By ~ 41

Author(s):

Dean A. Regier ◽

Jan M. Friedman ◽

Carlo A. Marra

Keyword(s):

Intellectual Disability ◽

Diagnostic Testing ◽

Value For Money ◽

Genomic Hybridization ◽

Genetic Causes

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Normocentric biases taint cognitive neuroscience and intervention of autism

Behavioral and Brain Sciences ◽

10.1017/s0140525x18002297 ◽

2019 ◽

Vol 42 ◽

Cited By ~ 1

Author(s):

Laurent Mottron

Keyword(s):

Intellectual Disability ◽

Cognitive Neuroscience ◽

Social Motivation ◽

Repetitive Behaviors ◽

Restricted Interests ◽

Autistic People

Abstract Stepping away from a normocentric understanding of autism goes beyond questioning the supposed lack of social motivation of autistic people. It evokes subversion of the prevalence of intellectual disability even in non-verbal autism. It also challenges the perceived purposelessness of some restricted interests and repetitive behaviors, and instead interprets them as legitimate exploratory and learning-associated manifestations.

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