Prenatal Diagnosis of Autosomal Recessive Primary Microcephaly Type 2 Caused by Compound Heterozygous WDR62 Variants
Yan-Fang Li1, Song-Hui Zhang1, Li Zhen2
1Department of Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Objective:
Autosomal recessive microcephaly type 2 (MCPH2), caused by biallelic WDR62 variants, is a rare neurodevelopmental disorder typically described postnatally. We aimed to delineate its prenatal phenotype via data from two affected fetuses in a family.
Methods:
Trio whole-exome sequencing (WES) was performed on one fetus and his parents. Variants were prioritized via population databases, computational predictions, and segregation analysis, which were confirmed via Sanger sequencing.
Results:
Prenatal imaging revealed microcephaly, agenesis of the corpus callosum, and neuronal migration defects (lobar holoprosencephaly and lissencephaly) in two fetuses. Trio-WES identified compound heterozygous WDR62 variants (c.1128C > A/p.Cys376* and c.643A > C/p.Thr215Pro) in one fetus, each inherited from a heterozygous parent. Sanger sequencing confirmed variants in both fetuses and parents.
Conclusions:
Trio-WES is crucial for the prenatal diagnosis of fetuses with unresolved sonographic anomalies. We report the prenatal features and molecular diagnoses of MCPH2, expanding its prenatal phenotypic spectrum and enhancing its clinical genomic database utility.
Insights
Microcephaly type 2 (MCPH2) prenatal diagnosis is aided by trio whole-exome sequencing (WES). This study details prenatal findings and WDR62 variants in two fetuses, expanding the understanding of this rare neurodevelopmental disorder.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Prenatal Diagnosis
Background:
- Autosomal recessive microcephaly type 2 (MCPH2) is a rare neurodevelopmental disorder.
- MCPH2 is typically diagnosed postnatally.
- The prenatal phenotype of MCPH2 requires further delineation.
Purpose of the Study:
- To characterize the prenatal phenotype of microcephaly type 2 (MCPH2).
- To identify the genetic cause of MCPH2 in affected fetuses.
- To assess the utility of trio whole-exome sequencing (WES) for prenatal diagnosis.
Main Methods:
- Trio whole-exome sequencing (WES) was performed on one affected fetus and parents.
- Variant prioritization utilized population databases, computational predictions, and segregation analysis.
- Sanger sequencing confirmed identified WDR62 variants.
Main Results:
- Prenatal imaging revealed microcephaly, agenesis of the corpus callosum, and neuronal migration defects in two fetuses.
- Trio-WES identified compound heterozygous WDR62 variants (c.1128C > A/p.Cys376* and c.643A > C/p.Thr215Pro) in one fetus.
- Variants were confirmed via Sanger sequencing in both fetuses and parents.
Conclusions:
- Trio-WES is essential for prenatal diagnosis of unexplained sonographic anomalies.
- This study expands the prenatal phenotypic spectrum of MCPH2.
- The findings enhance the utility of clinical genomic databases for MCPH2.
