The study developed a modified molecular inversion probe (MIP) method to enable ultra-low-cost candidate gene resequencing in large cohorts of autism spectrum disorder (ASD) probands. By sequencing 44 candidate genes in 2,446 ASD probands, the researchers identified 27 de novo mutations in 16 genes, with 59% predicted to truncate proteins or disrupt splicing. They estimated that recurrent disruptive mutations in six genes—*CHD8*, *DYRK1A*, *GRIN2B*, *TBR1*, *PTEN*, and *TBL1XR1*—may contribute to 1% of sporadic ASDs. The findings support associations between specific genes and reciprocal subphenotypes, such as macrocephaly with *CHD8* and microcephaly with *DYRK1A*, and highlight the importance of a β-catenin/chromatin remodeling network in ASD etiology. The MIP method provides a powerful tool for identifying rare variants and de novo mutations in complex disorders like ASD.The study developed a modified molecular inversion probe (MIP) method to enable ultra-low-cost candidate gene resequencing in large cohorts of autism spectrum disorder (ASD) probands. By sequencing 44 candidate genes in 2,446 ASD probands, the researchers identified 27 de novo mutations in 16 genes, with 59% predicted to truncate proteins or disrupt splicing. They estimated that recurrent disruptive mutations in six genes—*CHD8*, *DYRK1A*, *GRIN2B*, *TBR1*, *PTEN*, and *TBL1XR1*—may contribute to 1% of sporadic ASDs. The findings support associations between specific genes and reciprocal subphenotypes, such as macrocephaly with *CHD8* and microcephaly with *DYRK1A*, and highlight the importance of a β-catenin/chromatin remodeling network in ASD etiology. The MIP method provides a powerful tool for identifying rare variants and de novo mutations in complex disorders like ASD.