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Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next\u2010generation sequencing multi\u2010gene panel (i\u2010panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (<jats:italic>PAX6, SLC18A2, DSC3<\/jats:italic> and <jats:italic>CNKSR1<\/jats:italic>). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (<jats:italic>MYO10<\/jats:italic> and <jats:italic>ZNF219<\/jats:italic>), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition.<\/jats:p>","DOI":"10.1111\/cge.13239","type":"journal-article","created":{"date-parts":[[2018,2,16]],"date-time":"2018-02-16T09:52:35Z","timestamp":1518774755000},"page":"1210-1222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Genetic investigation of 93 families with microphthalmia or posterior microphthalmos"],"prefix":"10.1111","volume":"93","author":[{"given":"N.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center  Riyadh 11211 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.O.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital 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