A novel missense variant of HS6ST2 gene in Paganini-Miozzo syndrome with a rare neurodevelopmental and Endocrine...

Area of Science:

• Genetics and Molecular Biology
• Rare Diseases
• Neurodevelopmental Disorders

Background:

• Paganini-Miozzo syndrome (MRXSPM) is an X-linked disorder caused by mutations in the HS6ST2 gene.
• Globally, MRXSPM is exceptionally rare, with limited documented cases worldwide.
• Understanding the genetic basis and clinical spectrum of MRXSPM is crucial for diagnosis and management.

Purpose of the Study:

• To report the first case of Paganini-Miozzo syndrome in China.
• To identify and characterize a novel HS6ST2 gene mutation associated with MRXSPM.
• To investigate the functional impact of the identified mutation on HS6ST2 protein.

Main Methods:

• Whole exome sequencing (WES) was employed to identify genetic variants in the proband.
• Bioinformatics tools were used to predict the effect of the mutation on protein stability.
• In vitro cell experiments were conducted to assess the impact on HS6ST2 protein expression.

Main Results:

• A novel missense mutation, c.764C>A (p.Pro255Glu), in the HS6ST2 gene was identified in the Chinese proband.
• The mutation is predicted to affect HS6ST2 protein thermal stability and was observed to impact post-transcriptional expression.
• Clinical findings included developmental delay, mild lateral ventricular enlargement, and abnormal electroencephalogram and biochemical tests.

Conclusions:

• This study expands the geographic and genotypic spectrum of Paganini-Miozzo syndrome.
• The novel HS6ST2 mutation provides further insight into the molecular mechanisms underlying MRXSPM.
• Distinct HS6ST2 mutations may correlate with varying clinical phenotypes, highlighting the importance of precise genetic diagnosis.