A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and
Rosaria Nardello1, Antonina Fontana1, Vincenzo Antona2
1Child Neuropsychiatry Unit, Department of Sciences for Health Promotion and Mother and Child Care "G. D'Alessandro", University of Palermo, Palermo, Italy.
Abstract:
The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by head circumference of at least 3 standard deviation below the mean. The MCPH exhibits genetic heterogeneity with thirteen loci (MCPH1-MCPH13) identified, and associated with variable degree of intellectual disability. It has been reported that WDR62 is the second causative gene of autosomal recessive microcephaly (MCPH2) playing a significant role in spindle formation and the proliferation of neuronal progenitor cells. We report a clinical feature, electroclinical findings, and clinical course of a patient with a severe phenotype of MCPH2 including microcephaly, refractory infantile spasms and intellectual disability. Genetic analysis detected a new homozygous splicing variant c.3335+1G>C in the WD repeat domain 62 (WDR62) gene, inherited from both heterozygous healthy parents, and an additional new heterozygous missense mutation c.1706T>A of G protein-coupled receptor 56 (GPR56) gene inherited from his healthy father. The study seeks to broaden the knowledge of clinical and electroclinical findings of MCPH2 and to contribute to a better characterization of the genotype-phenotype correlation.
Insights
This study details a severe case of primary microcephaly (MCPH2), a rare brain development disorder. Researchers identified a new WDR62 gene variant, advancing understanding of MCPH2
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Primary microcephaly (MCPH) is a rare genetic disorder causing small head size and intellectual disability.
- MCPH exhibits genetic heterogeneity, with WDR62 identified as a key gene (MCPH2) involved in neuronal progenitor cell proliferation.
- Severe phenotypes of MCPH2, including microcephaly and refractory infantile spasms, require further clinical and genetic characterization.
Purpose of the Study:
- To report the clinical features, electroclinical findings, and clinical course of a patient with a severe phenotype of MCPH2.
- To identify novel genetic variants associated with MCPH2.
- To enhance the understanding of genotype-phenotype correlations in MCPH2.
Main Methods:
- Clinical case study.
- Electroencephalography (EEG) for electroclinical findings.
- Genetic analysis including whole exome sequencing and Sanger sequencing to identify mutations in WDR62 and GPR56 genes.
Main Results:
- A patient presented with severe microcephaly, refractory infantile spasms, and intellectual disability, consistent with MCPH2.
- Genetic analysis revealed a novel homozygous splicing variant (c.3335+1G>C) in the WDR62 gene.
- An additional novel heterozygous missense mutation (c.1706T>A) was identified in the GPR56 gene.
Conclusions:
- The findings expand the knowledge of clinical and electroclinical presentations in MCPH2.
- The identified WDR62 variant provides new insights into the genetic basis of primary microcephaly.
- This case contributes to a better characterization of genotype-phenotype correlations in WDR62-related microcephaly.
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