Cytogenetic abnormalities and fragile-X syndrome in Autism Spectrum Disorder

• Published in: BMC medical genetics 2005-01, Vol.6 (1), p.3-3, Article 3
• Main Author: Reddy, Kavita S
• Format: Article
• Language: English
• Subjects: Autistic Disorder - epidemiology; Autistic Disorder - genetics; Child, Preschool; Chromosome Aberrations - statistics & numerical data; Cytogenetic Analysis - methods; Female; Fragile X Mental Retardation Protein; Fragile X Syndrome - genetics; Humans; Male; Molecular Epidemiology - methods; Mutation - genetics; Nerve Tissue Proteins - genetics; RNA-Binding Proteins - genetics
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/1471-2350-6-3

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. 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. 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. 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.