Work

A CSPP1 variant associated with metabolic dysfunction in Joubert syndrome: a case report

Year: 2025

Type: article

Abstract: BACKGROUND: Joubert syndrome is a genetically heterogeneous ciliopathy characterized by cerebellar vermis hypoplasia and the distinctive molar tooth sign on neuroimaging, often accompanied by neurological impairment. Pathogenic CSPP1 variants account for approximately 3% of Joubert syndrome cases. While certain ciliopathies have been associated with metabolic dysfunction, this has not been described in CSPP1-related Joubert syndrome. CASE PRESENTATION: We report a 16-year-old Honduran mestiza female patient with CSPP1-related Joubert syndrome who presented with insulin resistance, early onset diabetes, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease. Notably, she lacked the typical neurological symptoms of Joubert syndrome. Brain magnetic resonance imaging revealed cerebellar vermis hypoplasia, confirming the diagnosis. Genetic testing identified a pathogenic heterozygous CSPP1 variant (c.3052C > T, p.Gln1018), supporting the diagnosis of CSPP1-related Joubert syndrome. CONCLUSION: This case expands the phenotypic spectrum of CSPP1-related Joubert syndrome and raises the possibility of a role for CSPP1 in metabolic homeostasis. Further research is needed to determine whether CSPP1 mutations contribute to metabolic dysfunction via ciliary or centrosome-associated mechanisms.

Source: Journal of Medical Case Reports

DOI: 10.1186/s13256-025-05332-w

Authors: Liany F. Acosta-Paguada, Milca S. Velásquez-Hernandez, Paola Sophia Bonilla Medina, Eduardo Smelin Perdomo Domínguez

Institution: Universidad Católica de Honduras Nuestra Señora Reina de la Paz

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,890