Tectonic gene mutations in patients with Joubert syndrome

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Tectonic genes (TCTN1-3) are implicated in rare ciliopathies.
• Sequence variants in these genes are infrequently reported.
• Joubert syndrome is a complex genetic disorder affecting brain development.

Observation:

• Two new patients with Joubert syndrome were identified using multi-gene panel next-generation sequencing (NGS).
• One patient had a TCTN3 splice-site variant; the other had a TCTN2 splice-site variant.
• Clinical data review confirmed a consistent neurological phenotype across TCTN1-3 variants.

Findings:

• Homozygous splice-site variants in TCTN3 and TCTN2 were identified in two Joubert syndrome patients.
• Tectonic gene variants primarily cause neurological issues like intellectual disability and vermis hypoplasia.
• Other common ciliopathy features were absent in patients with TCTN1-3 variants.

Implications:

• Comprehensive NGS panels are effective for diagnosing rare genetic disorders.
• Early and accurate genetic diagnosis can guide clinical management and reduce unnecessary testing.
• Understanding TCTN gene variants refines the spectrum of ciliopathy phenotypes.