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Novel compound heterozygous frameshift variants in WDR81 associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms WDR81 involvement
Novel compound heterozygous frameshift variants in WDR81 associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms WDR81 involvement
- Source :
- Molecular Genetics & Genomic Medicine, Molecular Genetics & Genomic Medicine, Vol 9, Iss 4, Pp n/a-n/a (2021)
- Publication Year :
- 2021
-
Abstract
- Background Congenital hydrocephalus‐3 with brain anomalies (HYC3, MIM 617967) is a rare form of congenital hydrocephalus characterized by severe hydrocephalus and cerebellar abnormalities, the onset of the disease occurs in utero even resulting in fetal death. A very limited spectrum of WDR81 pathogenic variants had been reported in three unrelated families with HYC3. This study aims at presenting novel compound heterozygous frameshift variants in WDR81 in a Chinese fetus. Methods Whole‐exome sequencing (WES) was performed for a fetus with multiple congenital anomalies including sever hydrocephalus, cleft lip and palate, hydrops fetalis, hepatomegaly, and cerebellar hypoplasia. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Results Two novel heterozygous variants c.146_147insG (p.Thr52fs) and c.673delC (p.Leu225fs) in WDR81 were identified. Sanger sequencing revealed that the c.146_147insG mutation was maternal origin and the c.673delC mutation was paternal origin. Both variants were pathogenic according to the ACMG/AMP guidelines. Conclusion The present study expands the mutation spectrum of WDR81 and help further define the genotype–phenotype correlations of HYC3. WDR81‐related HYC3 were highly clinical heterogeneity. We suggested that fetal hydrocephalus with extracerebral manifestations may be suggestive of WDR81 deficiency and WES is effective for achieving a conclusive diagnosis for disorder.<br />We identified a fetus with a Novel compound heterozygous frameshift variants in WDR81(c.146_147insG (p.Thr52fs) and c.673delC (p.Leu225fs)) presented with the main Congenital hydrocephalus 3 with brain anomalies (HYC3). This was a first Chinese prenatal case with HYC3 phenotype carried the WDR81 pathogenic variants detected by whole‐exon sequencing.
- Subjects :
- 0301 basic medicine
Adult
Pathology
medicine.medical_specialty
Heterozygote
prenatal
Nerve Tissue Proteins
QH426-470
030105 genetics & heredity
Compound heterozygosity
Frameshift mutation
03 medical and health sciences
symbols.namesake
Pregnancy
congenital hydrocephalus 3 with brain anomalies
Hydrops fetalis
Prenatal Diagnosis
Genetics
Medicine
Humans
Frameshift Mutation
Molecular Biology
Cerebellar hypoplasia
Genetics (clinical)
Sanger sequencing
Whole Genome Sequencing
business.industry
Molecular pathology
Brain
Original Articles
medicine.disease
WDR81
Hydrocephalus
030104 developmental biology
symbols
Medical genetics
Female
Original Article
compound heterozygous frameshift variants
business
Subjects
Details
- ISSN :
- 23249269
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular geneticsgenomic medicine
- Accession number :
- edsair.doi.dedup.....cf77858be37a01e79e16966c7ad885fa