Variability in the heterochromatin regions of the chromosomes and chromosomal anomalies in children with autism: Identification of genetic markers of autistic spectrum disorders

Abstract

Cytogenetic and molecular cytogenetic analysis of children with autism (90 subjects) and their mothers (18 subjects) is presented. Anomalies and fragility were found in chromosome X in four cases of autism: mos 47,XXX[98]/46, XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; and 46,Y,fra(X)(q27.3),16qh-. C staining and quantitative fluorescent in situ hybridization (FISH) were used to demonstrate a significant increase in the frequency of variations in the heterochromatin regions of chromosomes in children with autism as compared with a control group (48% and 16% respectively). Pericentric chromosome inversion 9phqh was not characteristic of patients with autism, while variation in heterochromatin regions 1phqh, 9qh+, and 16qh-were found significantly more frequently in children with autism. These data provide the basis for discussing the possible role of the gene position effect in the pathogenesis of autism and the possible search for biological markers of autistic disorders.

Molecular Cytogenetic Diagnosis and Somatic Genome Variations

“…Nevertheless, we would like to point some aspects relevant to the diagnosis. Firstly, we have to mention that it is really possible to achieve the resolution as high as 1% of cells affected by SGV or even lower [4, 28, 36-42]. The scoring of such a rare event as low-mosaicism is granted by approaches that include several molecular cytogenetic FISH-based techniques.…”

Genomic Instability in the Brain: Etiology, Pathogenesis and New Biological Markers of Psychiatric Disorders

“…Уровень соматической нестабильности, вероятно, уменьша-ется в ходе пренатального развития за счет селектив-ного отбора в пользу нормальных диплоидных клеток [9,22]. Экспериментальный анализ анеуплоидии в клетках спонтанных абортов и при некоторых болезнях мозга у детей подтверждает эти предположения [36,37]. Другая особенность CIN во время ранних стадий онтогенеза -способность ограничиваться (определенной) тканью.…”

“…В случае расстройств аутистического спектра были исследованы дети с недифференцированным аутизмом и синдромом Ретта (моногенное Х-сцепленное доминантное наслед-ственное заболевание известной этиологии, обуслов-ленное мутациями гена MECP2). Было обнаружено, что синдром Ретта (летальный для плодов мужского пола) может наблюдаться у мальчиков только при условии мозаичной/регулярной анеуплоидии хромосомы Х [13,37,54,[65][66][67][68]. При идиопатическом аутизме в 5% случаев наблюдались регулярные структурные и численные хромосомные аномалии [13], а в 16% -низкопроцентный мозаицизм, проявляющийся преимущественно в виде дополнительной хромосомы Х при мужском кариотипе [14].…”

Ontogenetic Variation of the Human Genome

“…Otherwise, a pathological condition is likely to occur [3, 8, 22]. Unfortunately, no direct evidences for this are, as yet, available, but analysis of spontaneous abortions and brain diseases in children supports these assumptions [8, 13, 15, 28, 29]. Another feature of CIN during early ontogeny stages is the ability to confine to a tissue.…”

“…This raises an important question about their origins. Firstly, GIN and CIN (aneuploidization) cause a wide spectrum of diseases both in childhood and in adulthood [8, 9, 11-18, 26, 29, 33-35]. Additionally, some GIN/CIN signatures such as uniparental disomy due to intrauterine trisomy rescue via confined placental mosaicism [46] and low-level chromosomal mosaicism in child and adult individuals [3, 8, 9, 34] have been reported.…”