PMID- 15655077
OWN - NLM
STAT- MEDLINE
DCOM- 20050208
LR  - 20240317
IS  - 1471-2350 (Electronic)
IS  - 1471-2350 (Linking)
VI  - 6
DP  - 2005 Jan 18
TI  - Cytogenetic abnormalities and fragile-X syndrome in Autism Spectrum Disorder.
PG  - 3
AB  - 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.
FAU - Reddy, Kavita S
AU  - Reddy KS
AD  - Genzyme Genetics, Orange CA 92868, USA. kavita.reddy@gmail.com
LA  - eng
PT  - Journal Article
DEP - 20050118
PL  - England
TA  - BMC Med Genet
JT  - BMC medical genetics
JID - 100968552
RN  - 0 (FMR1 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
SB  - IM
MH  - Autistic Disorder/*epidemiology/*genetics
MH  - Child, Preschool
MH  - Chromosome Aberrations/*statistics & numerical data
MH  - Cytogenetic Analysis/*methods
MH  - Female
MH  - Fragile X Mental Retardation Protein
MH  - Fragile X Syndrome/*genetics
MH  - Humans
MH  - Male
MH  - Molecular Epidemiology/methods
MH  - Mutation/genetics
MH  - Nerve Tissue Proteins/genetics
MH  - RNA-Binding Proteins/genetics
PMC - PMC548305
EDAT- 2005/01/19 09:00
MHDA- 2005/02/09 09:00
PMCR- 2005/01/18
CRDT- 2005/01/19 09:00
PHST- 2004/08/08 00:00 [received]
PHST- 2005/01/18 00:00 [accepted]
PHST- 2005/01/19 09:00 [pubmed]
PHST- 2005/02/09 09:00 [medline]
PHST- 2005/01/19 09:00 [entrez]
PHST- 2005/01/18 00:00 [pmc-release]
AID - 1471-2350-6-3 [pii]
AID - 10.1186/1471-2350-6-3 [doi]
PST - epublish
SO  - BMC Med Genet. 2005 Jan 18;6:3. doi: 10.1186/1471-2350-6-3.