Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in <b><i>ASPM</i></b> and <b><i>WDR62</i></b> Genes

Abstract

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Autosomal recessive primary microcephaly (MCPH) is a disorder characterized by congenital microcephaly and intellectual disability without extra-central nervous system malformation. MCPH is a disease with heterogeneity in genotype and phenotype. For this reason, it is important to determine the genetic causes and genotype-phenotype relationship in MCPH, which causes lifelong impairment. In this study, we aimed to evaluate the clinical, genetic, and brain imaging findings of cases diagnosed with MCPH. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Electroencephalogram and brain magnetic resonance imaging were performed for all cases. We evaluated genetic results of the 39 families including cases with suspected MCPH diagnosis. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Genetic diagnosis related to MCPH was provided in 11/39 (28.2%) of these families including 13/41 cases (31.7%). Variants of the &lt;i&gt;WDR62&lt;/i&gt; gene were the most common (61.5%) cause, and variants of the &lt;i&gt;ASPM&lt;/i&gt; gene were the second most common cause (38.5%). We have found 6 novel variants and 4 previously reported variants in &lt;i&gt;ASPM&lt;/i&gt; and &lt;i&gt;WDR62&lt;/i&gt; genes. Main brain imaging findings in our cases were lissencephaly, polymicrogyria, schizencephaly, pachygyria, and cortical dysplasia. Genetic counseling in 2 families whose genetic diagnosis was determined prevented them from having another child with MCPH. &lt;b&gt;&lt;i&gt;Discussion/Conclusion:&lt;/i&gt;&lt;/b&gt; Detection and reporting of novel variants is an important step in eliminating this disorder by providing families with appropriate genetic counseling.