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Cited by 222Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchGenomic variations and chromosomal abnormalities

The DOI matches its Crossref record; 114 of the 123 references it cites were found in a registry or an index.

Cytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder

Open access
Reddy, Kavita S·2005·BMC Medical Genetics
DOI 10.1186/1471-2350-6-3PMC PMC548305
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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.

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Figure 1 Chromosome abnormalities in patients with autistic traits (A) 4 markers: [multiple copies] derived from chromosome 2 [1], 15 [3] with nomenclature (B) 1 duplication of chromosome 15 with arrow denoting the region involved (C) 3 partial deletions (right homolog)(multiple copies) of 3p25, 12q21.2q23.3 & 13q13.2q14.1 with the ideogram, the arrows denote the deleted region. (D) 3 inversions (the right homolog) (multiple copies), inv(10)(p11.2q21.2), inv(14)(q11.2q32), inv(17)(q24.2q25.3) with arrows on the ideogram showing the inverted region (E) 2 translocations (partials in 2 copies, chromosomes involved (right) and their normal homolog (left)) one apparently balanced t(1;14)(q25;q31.2) and one unbalanced der(14;18)(q10;q10). The ideogram with arrows show the breakpoints
Figure 1 Chromosome abnormalities in patients with autistic traits (A) 4 markers: [multiple copies] derived from chromosome 2 [1], 15 [3] with nomenclature (B) 1 duplication of chromosome 15 with arrow denoting the region involved (C) 3 partial deletions (right homolog)(multiple copies) of 3p25, 12q21.2q23.3 & 13q13.2q14.1 with the ideogram, the arrows denote the deleted region. (D) 3 inversions (the right homolog) (multiple copies), inv(10)(p11.2q21.2), inv(14)(q11.2q32), inv(17)(q24.2q25.3) with arrows on the ideogram showing the inverted region (E) 2 translocations (partials in 2 copies, chromosomes involved (right) and their normal homolog (left)) one apparently balanced t(1;14)(q25;q31.2) and one unbalanced der(14;18)(q10;q10). The ideogram with arrows show the breakpointsCC BY · PubMed Central
Figure 2 Mosaic fragile X mutations: Southern blot using probe StB12.3 on EcoR1 and Eag1 (methylation-sensitive enzyme) digested DNA. Lane 1 – permutation carrier, Lane 2 & 3 – normal female, Lane 4 – normal male, Lane 5 – an ASD male mosaic with fm (3.7 and 5.8–7.9 kb, 200–900 r)(arrows)/a deletion mutation (2.8 kb faint band, 30 r)(arrow). By PCR a 30 repeats and >200 repeats were amplified. Lane 6 – an ASD male mosaic fm (6.4 kb, 400 r)/pm (3.3 kb, 150 r).
Figure 2 Mosaic fragile X mutations: Southern blot using probe StB12.3 on EcoR1 and Eag1 (methylation-sensitive enzyme) digested DNA. Lane 1 – permutation carrier, Lane 2 & 3 – normal female, Lane 4 – normal male, Lane 5 – an ASD male mosaic with fm (3.7 and 5.8–7.9 kb, 200–900 r)(arrows)/a deletion mutation (2.8 kb faint band, 30 r)(arrow). By PCR a 30 repeats and >200 repeats were amplified. Lane 6 – an ASD male mosaic fm (6.4 kb, 400 r)/pm (3.3 kb, 150 r).CC BY · PubMed Central
Figure 3 Chromosome 15q11-q13 region showing the autism candidate region. A schematic representation of the 15q11-q13 interval duplicated in autism cases and deleted in Prader-Willi/Angelman syndrome is shown. IC denotes the position of the 15q imprinting center. Loci corresponding to previous reports of linkage and association are indicated by dark and light arrowheads, respectively, below the map. (Adapted with permission from Sutcliffe J et al article "Dense linkage disequilibrium mapping in the 15q11-q13 maternal expression domain yields evidence for association in autism' in Molecular Psychiatry (2003) 8, 624–634)
Figure 3 Chromosome 15q11-q13 region showing the autism candidate region. A schematic representation of the 15q11-q13 interval duplicated in autism cases and deleted in Prader-Willi/Angelman syndrome is shown. IC denotes the position of the 15q imprinting center. Loci corresponding to previous reports of linkage and association are indicated by dark and light arrowheads, respectively, below the map. (Adapted with permission from Sutcliffe J et al article "Dense linkage disequilibrium mapping in the 15q11-q13 maternal expression domain yields evidence for association in autism' in Molecular Psychiatry (2003) 8, 624–634)CC BY · PubMed Central
Figure 4 The map location of D15S11 probe used to characterize the markers
Figure 4 The map location of D15S11 probe used to characterize the markersCC BY · PubMed Central

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Cites

Show all 123 references

Research works printed but not linked: 9

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  2. Wolff DJ, Clifton K, Karr C, Charles J: Pilot assessment of the subtelomeric regions of children with autism: detection of a 2q deletion. Genet Med. 2002, 4: 10-4. 10.1097/00125817-200201000-00002. · DOI
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Metadata

Authors
Reddy, K. S.
Corresponding author
Reddy, Kavita S
Venue
BMC Medical Genetics
Publisher
Springer Science and Business Media LLC
Published
2005-01-18
Volume
6
Issue
1
Pages
3-3
ISSN
1471-2350 (ISSN-L)
DOI
10.1186/1471-2350-6-3
PMC
PMC548305
OpenAlex
W1493214217
Cited by
222
References
123
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 15 · 2020: 11 · 2019: 6 · 2018: 4 · 2017: 9 · 2016: 13 · 2015: 10 · 2014: 15 · 2013: 23 · 2012: 15
FWCI
5.93
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medical Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
autism spectrum disorder, fragile X syndrome, chromosomal abnormalities, fragile X premutation, chromosome 15q11-q13, chromosome 2q37, fluorescence in situ hybridization, karyology, idiopathic autism, translocation
MeSH terms
Autistic Disorder, Child, Preschool, Chromosome Aberrations, Female, Fragile X Syndrome, Humans, Male, Mutation, Nerve Tissue Proteins, RNA-Binding Proteins, Molecular Epidemiology, Cytogenetic Analysis, Fragile X Messenger Ribonucleoprotein 1

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