History of Autism Becoming a Genetic Disease 151included in the ASD group of disorders. Children with Rett syndrome suffer
from epileptic seizures, gait ataxia, and stereotypical hand movements. These
twins shared the same de novo mutation in exon 4 of the MECP2 gene
(G269AfsX288), which was paternal in origin and occurred during spermato-
genesis. The X chromosome inactivation patterns in the twins did not differ in
lymphocytes, skin fibroblasts, and hair cells (which originate from ectoderm as
does neuronal tissue). No differences were detected between the twins in sin-
gle nucleotide polymorphisms (SNPs), insertion‐deletion polymorphisms
(indels), or copy number variations (CNVs). Differences in DNA methylation
between the twins were detected in fibroblasts in the upstream regions of
genes involved in brain function and skeletal tissues such as Mohawk
Homeobox (MKX), Brain‐type Creatine Kinase (CKB), and FYN Tyrosine
Kinase Protooncogene (FYN). The level of methylation in these upstream
regions was inversely correlated with the level of gene expression. Thus, differ-
ences in DNA methylation patterns likely underlie the discordance in Rett
phenotypes between the twins.
In addition, they describe in detail the relationship between neurodevelop-
mental disorders and environmental toxicants, in particular plastic‐derived
chemicals (bisphenol A and phthalates), persistent organic pollutants, heavy
metals, and maternal smoking.
Differences in CNV between Discordant Monozygotic Twins
with Congenital Heart Defects
Breckpot et al. [26,27] explored the occurrence of copy number differences in
monozygotic twins discordant for the presence of a congenital heart defect
(CHD). They carried out an array comparative genomic hybridization on
peripheral blood‐derived DNA from six discordant monozygotic twin pairs
and on sex‐matched reference samples. To identify somatic CNV/differences
between both twin members as well as potential CNVs in both twins contrib-
uting to the CHD, they analyzed the DNA from each twin by hybridizing
against its co‐twin, and against a normal control. They detected three copy
number differences in one out of six monozygotic twin pairs, confirming the
occurrence of somatic CNV events in monozygotic twins. This report empha-
sizes the postzygotic genetic, environmental and stochastic factors that can
affect human heart development.
History of Autism Becoming a Genetic Disease
Until 1976, autism was not considered a genetic disease. In 1976, Hanson et al.
published a comprehensive review [28]. They found no convincing evidence of
a genetic role in the etiology of autism. “No strong evidence exists,” they