[HEXB gene study and prenatal diagnosis for a family affected by infantile Sandhoff disease]
Tongfei Wu1, Xiyuan Li, Qiao Wang
1Department of Pediatrics, Peking University First Hospital, Beijing 100034.
Insights
This study investigated infantile Sandhoff disease in a Chinese family, identifying a novel HEXB gene mutation. Prenatal diagnosis confirmed the fetus was unaffected, ensuring a healthy sibling was born.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Infantile Sandhoff disease is a rare, fatal neurodegenerative lysosomal storage disorder.
- It results from mutations in the HEXB gene, leading to deficient beta-hexosaminidase activity.
- Early diagnosis and genetic counseling are crucial for affected families.
Observation:
- A Chinese boy presented with progressive psychomotor regression, seizures, and severe developmental delay.
- Clinical findings included cherry-red spots, optic atrophy, and white matter abnormalities on MRI.
- Significantly deficient beta-hexosaminidase activity confirmed Sandhoff disease.
Findings:
- Two HEXB gene mutations were identified: a novel mutation (c.1645G-A, p.G549R) and a previously reported one (c.IVS7-48T).
- Prenatal diagnosis using amniocyte gene analysis revealed the fetus carried neither mutation.
- A healthy sibling was born, with postnatal tests confirming the prenatal diagnosis.
Implications:
- Identification of a novel HEXB mutation expands the known mutation spectrum for Sandhoff disease.
- Successful prenatal diagnosis facilitated informed reproductive choices for the family.
- This case highlights the importance of integrated enzymatic and genetic testing for Sandhoff disease diagnosis and management.
Objective:
To investigate the phenotype and genotype of a Chinese boy and his family affected by infantile Sandhoff disease.
Methods:
The proband, a boy, was the first child born to a non-consanguineous couple. He showed startle reaction after birth and progressive psychomotor regression from the age of 8 months. From the age of 16 months, he presented seizures. When he was admitted at 17 months old, severe mental retardation and weakness were observed. Fundus examination revealed bilateral cherry-red spots in the macula and optic atrophy. Cranial MRI revealed abnormal signals in the thalamus, basal ganglia and white matter. Enzymatic assay and genetic testing were performed for the diagnosis. His mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene diagnosis to the fetus was performed by direct sequencing.
Results:
Significant deficient total β-hexosaminidase (A and B) activity in peripheral leucocytes of the patient (0.0 nmol/h/mg compared with normal control, 41.9 to 135.1 nmol/h/mg) supported the diagnosis of Sandhoff disease. On his HEXB gene, two mutations were found. c.1645G-A (p.G549R) was novel. c.IVS7-48T was a reported mutation. Now, the patient was 2 years and 3 months old, with progressive general failure, severe epilepsy, blindness and hypermyotonia. Subsequently, the mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene analysis of the amniocytes was performed by direct sequencing. Both of the two mutations were not detected from cultured amniocytes. The result revealed that the fetus was not affected by Sandhoff disease. A healthy girl, the sibling of the proband, was born in term. Postnatal enzyme analysis and genetic analysis of the cord blood cells confirmed the prenatal diagnosis.
Conclusion:
One novel mutation on HEXB gene was identified. Prenatal diagnosis to the fetus of this family was performed by amniocytes gene analysis.
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