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Identification of novel variants in BRF1 gene from patient with developmental delay, hearing abnormality, and nervous
Hongwei Yin1, Yonglin Yu1, Yingying Shen2
1Department of Rehabilitation, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, China.
Insights
Cerebellofaciodental syndrome, linked to BRF1 gene variants, can cause developmental delay and hearing loss. Rehabilitation may not be effective, suggesting alternative treatments are needed for affected children.
Area of Science:
- Genetics
- Neurology
- Developmental Biology
Background:
- Cerebellofaciodental syndrome presents with intellectual disability and brain anomalies.
- The syndrome's clinical spectrum now includes hearing impairment and inner ear malformations.
Observation:
- A 14-month-old boy exhibited global developmental delay and hearing disorder.
- Brain MRI revealed cerebellar hypoplasia, enlarged cisterna magna, and a prominent fourth ventricle.
Findings:
- Whole exome sequencing identified compound heterozygous variants in the BRF1 gene (c.652 T>G and c.915+1G>T).
- These variants were inherited from both parents.
Implications:
- This expands the known genetic spectrum of BRF1 variants.
- Patients with BRF1-related developmental delay may require treatments beyond conventional rehabilitation therapy.
Abstract:
Cerebellofaciodental syndrome characterized with dysmorphic features, intellectual disability, and brain anomalies. Now its clinical spectrum expanded more manifestations including bilateral sensorineural hearing impairment and inner ear malformation. Here, we report a 14-month-old boy with global developmental delay and hearing disorder. Whole exome sequencing (WES) revealed the compound heterozygous variants [NM_001519.4: c.652 T > G (p.W218G); c.915 + 1G > T] in the BRF1 gene which inherited from his parents, respectively. The MRI results showed hypoplastic cerebellar vermis, enlarged cisterna magna, and prominent fourth ventricle, the rehabilitation therapy failed to improve the symptoms for our patient. Our finding expands the genetic spectrum of BRF1 variants, which indicates patients with the developmental delay caused by BRF1 variants require other treatments instead of rehabilitation.
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