Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes.
BACKGROUND: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetica...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2878316?pdf=render |
| _version_ | 1811208396645335040 |
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| author | Hilgo Bruining Leo de Sonneville Hanna Swaab Maretha de Jonge Martien Kas Herman van Engeland Jacob Vorstman |
| author_facet | Hilgo Bruining Leo de Sonneville Hanna Swaab Maretha de Jonge Martien Kas Herman van Engeland Jacob Vorstman |
| author_sort | Hilgo Bruining |
| collection | DOAJ |
| description | BACKGROUND: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. METHODOLOGY: The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. PRINCIPAL FINDINGS: The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. CONCLUSION: The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population. |
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| format | Article |
| id | doaj.art-e0af5ef5f3cd491188ab0c403c99376b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T04:20:32Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e0af5ef5f3cd491188ab0c403c99376b2022-12-22T03:48:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0155e1088710.1371/journal.pone.0010887Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes.Hilgo BruiningLeo de SonnevilleHanna SwaabMaretha de JongeMartien KasHerman van EngelandJacob VorstmanBACKGROUND: The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. METHODOLOGY: The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. PRINCIPAL FINDINGS: The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. CONCLUSION: The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.http://europepmc.org/articles/PMC2878316?pdf=render |
| spellingShingle | Hilgo Bruining Leo de Sonneville Hanna Swaab Maretha de Jonge Martien Kas Herman van Engeland Jacob Vorstman Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. PLoS ONE |
| title | Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. |
| title_full | Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. |
| title_fullStr | Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. |
| title_full_unstemmed | Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. |
| title_short | Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes. |
| title_sort | dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes |
| url | http://europepmc.org/articles/PMC2878316?pdf=render |
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