Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in ASPM and WDR62 Genes

• Published in: Molecular syndromology Vol. 13; no. 5; pp. 363 - 369
• Main Authors: Bolat, Hilmi, Sağer, Safiye G., Türkyılmaz, Ayberk, Çebi, Alper H., Akın, Yasemin, Onay, Hüseyin, Özkınay, Ferda, Ünsel-Bolat, Gül
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.12.2022
• Subjects: Original; Original Article; ASPM; Novel variant; Autosomal recessive; MCPH; WDR62; Whole-exome sequencing
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000524391

Introduction: 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. Methods: 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. Results: Genetic diagnosis related to MCPH was provided in 11/39 (28.2%) of these families including 13/41 cases (31.7%). Variants of the WDR62 gene were the most common (61.5%) cause, and variants of the ASPM gene were the second most common cause (38.5%). We have found 6 novel variants and 4 previously reported variants in ASPM and WDR62 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. Discussion/Conclusion: Detection and reporting of novel variants is an important step in eliminating this disorder by providing families with appropriate genetic counseling.