Author(s): Reddy KS
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Abstract BACKGROUND: Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5-10 \% of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. METHODS: Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH) and/or molecular testing for fragile X syndrome by Southern and PCR methods. RESULTS: The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs) abnormality was found in 14/421 [3.33 \%] cases. The aberrations were: 4/14 [28\%] supernumerary markers; 4/14 [28\%] deletions; 1/14 [7\%] duplication; 3/14 [21\%] inversions; 2/14 [14\%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 \%] with an abnormal result. The mutations detected were: a full mutation (fM) and abnormal methylation in 3 [43 \%], mosaic mutations with partial methylation of variable clinical significance in 3 [43\%] and a permutation carrier [14\%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7\%, FRAX 2-4\%). Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. CONCLUSIONS: Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23.3 region should be standard practice when the indication is autism. The higher incidence of mosaic fragile-X mutations with partial methylation compared to FRAXA positive population [50\% vs 15-40\%] suggests that faint bands and variations in the Southern band pattern may occur in autistic patients.
This article was published in BMC Med Genet
and referenced in Journal of Psychiatry