Novel Mutations in KCNJ10 Gene Associated With SeSAME Syndrome: Rare Disorder With Possible Common Mutation

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Human Physiology

Background:

• SeSAME syndrome is an autosomal recessive disorder caused by mutations in the KCNJ10 gene.
• KCNJ10 encodes the Kir4.1 potassium channel, crucial for maintaining potassium homeostasis.
• Symptoms include seizures, sensorineural deafness, ataxia, intellectual impairment, and electrolyte imbalances.

Purpose of the Study:

• To investigate the genetic basis of SeSAME syndrome in three Iranian families.
• To identify novel KCNJ10 mutations and analyze their impact on Kir4.1 channel function.
• To enhance understanding of the genotype-phenotype correlation in SeSAME syndrome.

Main Methods:

• Whole-exome sequencing (WES) was performed on affected individuals from three families.
• Segregation analysis and Sanger sequencing confirmed the identified KCNJ10 variants.
• Bioinformatic tools were used for pathogenicity prediction and structural modeling of Kir4.1.

Main Results:

• Two novel KCNJ10 mutations, c.967T>C (p.Y323H) and c.352G>A (p.A118T), were identified.
• Affected individuals presented with early-onset seizures, ataxia, developmental delays, and hearing abnormalities.
• Structural modeling indicated that both mutations affect Kir4.1 channel stability and function.

Conclusions:

• The study expands the spectrum of known KCNJ10 mutations associated with SeSAME syndrome.
• The findings provide valuable insights into the genotype-phenotype correlation for SeSAME syndrome.
• Understanding these mutations aids in diagnosing and potentially managing SeSAME syndrome.