An Indian child with Coats plus syndrome due to mutations in STN1

Area of Science:

• Genetics
• Molecular Biology
• Ophthalmology

Background:

• The CTC1-STN1-TEN1 (CST) complex is crucial for telomere maintenance and genome stability.
• Coats plus syndrome (CP) is a rare genetic disorder characterized by telomeropathy and other severe symptoms.
• Understanding the genetic basis of CP is vital for diagnosis and potential therapeutic strategies.

Observation:

• An Indian child presented with clinical features of CP, including retinal exudates, cerebral calcification, developmental delay, and chronic gastrointestinal bleeding.
• Whole exome sequencing identified compound heterozygous variants in the STN1 gene.
• One variant was a known nonsense variant (p.Arg133*), while the second (p.Ala329Pro) was novel.

Findings:

• The novel p.Ala329Pro variant in STN1 was investigated using molecular dynamics simulations.
• Simulations indicated that this mutation disrupts the interaction within the C-terminal domain of the STN1-TEN1 complex.
• This disruption likely contributes to the pathogenesis of CP in the affected child.

Implications:

• This case expands the known spectrum of STN1 variants associated with Coats plus syndrome.
• The findings highlight the importance of genetic analysis in diagnosing complex pediatric disorders.
• Hormonal therapy showed a transient, modest benefit in reducing transfusion needs, suggesting avenues for further investigation.