BAD Oncology id/name DOID:0060041
Curation Status: Complete
|25363768)||Iossifov I et al. (2014) performed whole exome sequencing on simplex families from the Simon Simplex Collection (SSC), each having a child with an autistic spectrum disorder: in total, there were 2,508 affected children, 1,911 unaffected siblings and the parents of each family. Detailed and standardized phenotypic analysis were obtained and reported. By comparing affected to unaffected siblings, this study showed that 13% of de novo missense mutations and 43% of de novo likely gene disrupting (LGD) mutations (nonsense, frameshift and splice site) contribute to 12% and 9% of diagnoses, respectively. LGD mutations in about 400 genes are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes. LGD mutations occur at significantly higher rates in affected versus unaffected siblings, gene disrupting mutations (nonsense, splice site and frame shifts) are twice as frequent (PMID: 22542183 ). A male proband with verbal IQ of 42 and nonVerbal IQ of 104, from a simplex Asian Family 12950, had a de novo frame shift deletion of 7:138968839:CCTCT:C/ 3188+CTCT/1063-!. The male sibling without autism does not have this LGD.|
|28263302||Yuen RKC et al.(2017) reported whole genome sequencing (WGS) of 5205 unique samples (5193 individuals) from unique families with children diagnosed with Autism Spectrum Disorder (ASD). This study identified 61 ASD risk genes, of which, 18 are new ASD-risk genes including UBN2 gene. They found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability of ASD cases. Proband from a multiplex family 2-0057-004 had a de novo exonic stop gain mutation UBN2:NM_173569:exon10:c.1735C>T:p.Arg579Ter. The phenotype includes infrequent asthma, tubes in ears, slight heart murmur in addition to autism.|
NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.