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However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype\u2010specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype\u2010to\u2010genotype approach, we performed whole\u2010exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head\u2010size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (\n                    <jats:italic>PTEN<\/jats:italic>\n                    ,\n                    <jats:italic>CHD8<\/jats:italic>\n                    ) in this small cohort. De novo mutations in several candidate genes (\n                    <jats:italic>UBN2<\/jats:italic>\n                    ,\n                    <jats:italic>BIRC6<\/jats:italic>\n                    ,\n                    <jats:italic>SYNE1<\/jats:italic>\n                    , and\n                    <jats:italic>KCNMA1<\/jats:italic>\n                    ) were detected, as well as one new candidate gene (\n                    <jats:italic>TNPO3<\/jats:italic>\n                    ) implicated in ASD and related neurodevelopmental disorders. We identify genotype\u2010phenotype correlations for head\u2010size\u2010associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype\u2010to\u2010genotype strategy would accelerate the elucidation of genotype\u2010phenotype relationships for ASD by using phenotype\u2010restricted cohorts.\n                  <\/jats:p>","DOI":"10.1111\/cge.13665","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T03:14:32Z","timestamp":1572578072000},"page":"338-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Phenotype\u2010to\u2010genotype approach reveals head\u2010circumference\u2010associated genes in an autism spectrum disorder cohort"],"prefix":"10.1111","volume":"97","author":[{"given":"Huidan","family":"Wu","sequence":"first","affiliation":[{"name":"Center for Medical Genetics &amp; Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences Central South University  Changsha 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Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglei","family":"Xun","sequence":"additional","affiliation":[{"name":"Mental Health Center of Shandong Province  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Developmental Disorders in Children Liuzhou Maternity and Child Healthcare Hospital  Liuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Children Psychology and Behavior Third Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqin","family":"Duan","sequence":"additional","affiliation":[{"name":"Center of Children Psychology and Behavior Third Affiliated Hospital of Zhengzhou University  Zhengzhou 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