GENETICKÁ STUDIE DVACETI PACIENTŮ S PORUCHAMIAUTISTICKÉHO SPEKTRA

Genetic Study of Twenty Patients with Autism Spectrum Disorders

Background.
Many observations indicate that genetic factors play an important role in the aetiology of autism.Up to now, however, no genetic markers have been convincingly identified which influence the predisposition tothis disorder. Complex genetic analysis of autistic patients and their families may therefore lead to the identificationof features which could help to direct further search for the predisposing genes.Methods and Results. We have analysed a sample of 20 patients with autism spectrum disorders. The patientshave been subjected to clinical genetic examination, cytogenetic analysis and DNA analysis of the FMR1 gene. Inthe sample studied we have observed more boys (15/20), various degree ofmental retardation (18/20), high frequencyof complications during pregnancy (10/20) and delivery (10/20), increased incidence of psychiatric disorders,behavioural abnormities and suicides among the relatives, and increased head circumference and unusually formedears in the probands. Three patients had different chromosomal aberrations or variants (t(21;22), inv(9) and inv(10)).One patient harboured expansion of the trinucleotide repeat sequence in the FMR1 gene on the full mutation levelwhich is characteristic for the fragile X syndrome, and one patient is suspected to suffer from the Rett syndrome.Conclusions. Our observations confirm and extend the results reported in the literature.Most interesting aremainlythe macrocephaly which may be associated with the recently described increased neonatal levels of neural growthfactors in autistic individuals, ear malformations which may indicate aberrations in the HOXA1 gene pathway, theoccurrence of chromosomal inversions recurrent in autism, and peculiarities in the pedigrees of the patients.

Key words:
autism, pregnancy complications, genetic load, macrocephaly, ear shape abnormalities, chromosomalinversions, FMR1 gene, fragile X syndrome, Rett syndrome.