Many published reports in which copy number variants have been identified include information on the individuals (also referred to as cases or probands) with autism. When provided, this information is curated and presented in the individual data section.
Case studies commonly feature detailed profiles on affected individuals from which we extract information to form the following categories:
This category can potentially contain a broad range of information, depending on the source material, including: clinical history; dysmorphic features; comorbidities commonly associated with ASD, such as ADHD, epilepsy, or sleep disturbances; and growth parameters including height, weight, and head circumference. When included in the published report, ADI-R and/or ADOS scores are also listed. Otherwise, more qualitative measures of core ASD features (deficiencies in social interactions, communication deficits, and repetitive and restricted behaviors) are provided.
Individuals with ASD often exhibit a range of intellectual deficits. Information on IQ scores or the extent of mental retardation, intellectual disability, or developmental delay are provided in this category. A cognitive profile may either be qualitative (``average,`` ``below-average,`` etc.) or quantitative (with a numerical score or percentile values), and in some cases the testing methodology is provided.
In addition, many published reports also feature the following information:
A CNV can arise de novo or be inherited through either the maternal or paternal chromosomes. (In some cases, a CNV can be inherited from both parents). A de novo CNV spontaneously arises in an individual and is not transmitted from either parent, and there is considerable interest in the importance of de novo CNVs as a significant genetic cause for ASD, especially in simplex families. However, both maternally-inherited and paternally-inherited CNVs are also believed to confer varying degrees of pathogenic risk. If the origin of a CNV has not been ascertained, then its inheritance is classified in the module as ``Unknown.``
Of particular importance in assessing the clinical significance of any given copy number variant is how closely the CNV associates or segregates with the disorder. For example, if a copy number variant is only identified in one or more siblings with autism, but it is not present in any unaffected siblings, the CNV is said to segregate with the disorder However, if a copy number variant is found in an individual with autism and at least one of his or her unaffected siblings, or if a CNV is present in one sibling with autism but not in another affected sibling, then the CNV-disease association is characterized as not segregating. By their nature, de novo CNVs are considered to closely segregate with the disorder.
In many cases, families with individuals who have autism are categorized as either simplex or multiplex. In a simplex family, the proband identified in a CNV report is the only sibling in that family with ASD. (Simplex cases may also be referred to as sporadic cases in some scientific literature.) In a multiplex family, there is at least one sibling with autism in the proband's family in addition to the individual identified in a CNV report. When such information is provided, the Family Profile is listed as either Simplex or Multiplex. This information is essential in understanding how closely a given CNV co-segregates with the disorder.
Each entry in the CNV module dataset is assigned a name (or patient ID) that consists of the name of the cohort to which the individual belongs, followed by a unique identification tag that differentiates that person from other probands in the same cohort. In many cases, the unique identification tag used in the dataset is taken directly from the patient identification tag in the original report. Otherwise, the individual is assigned an identification tag during the annotation process.
For example, for patient 5335_3 from the ASD discovery case cohort described in Pinto D 2010, the name of the individual in the module would be:?pinto_10_ASD_discovery_cases-case5335_3.
# of Individuals by Diagnosis
CNV Validation in ASD Cases
As individual algorithms that predict the presence of a CNV can have a high false discovery rate, we distinguish between those that have been validated by an independent method or algorithm from those that have not. Unvalidated CNVs are included so as to provide the most comprehensive listing of potential CNVs as possible.