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

Bolat H., Saǧer S. G., TÜRKYILMAZ A., ÇEBİ A. H., Akln Y., Onay H., ...More

Molecular Syndromology, vol.13, no.5, pp.363-369, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 5
  • Publication Date: 2022
  • Doi Number: 10.1159/000524391
  • Journal Name: Molecular Syndromology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
  • Page Numbers: pp.363-369
  • Keywords: MCPH, Whole-exome sequencing, Novel variant, Autosomal recessive, ASPM, WDR62, MUTATIONS, GENETICS
  • Karadeniz Technical University Affiliated: Yes


© 2022 S. Karger AG, Basel.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.