Impact of D-bifunctional Protein Deficiency on Telomere Length and Gene Expression in a Child
Marta Elena Hernández-Caballero *
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, C.P.11340, Mexico.
Diego Julio Arenas-Aranda
Unidad de Investigación Médica en Genética Humana, Centro Médico Nacional Siglo XXI (CMN SXXI), Instituto Mexicano del Seguro Social (IMSS), Mexico City, C.P. 06720, Mexico.
Raquel Chávez-Torres
Hospital Pediatrico Peralvillo, Secretaría de Salud, Mexico City, C.P.6920, Mexico.
José Alfredo Sierra-Ramírez
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, C.P.11340, Mexico.
Calzada-Mendoza Claudia Camelia
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, C.P.11340, Mexico.
*Author to whom correspondence should be addressed.
Abstract
Aim: To explore, in one patient, the possibility that D-bifunctional protein (D-BP) deficiency affects telomere length, and to determine the profile of genetic expression.
Presentation of Case: Due to the symptoms of a newborn and his family background, a peroxisomal panel was performed. There were high levels of very long chain fatty acids and abnormal peroxisomes. At 8 months the patient exhibited other complications, including progressive multi systemic deterioration, and at 15 months died of pneumonia.
Discussion: Analysis of the patient’s fibroblasts provided evidence of a defect in the peroxisomes and in the oxidation of fatty acids, leading to a diagnosis of D-BP deficiency. Significant alterations were found in the genetic expression profile, with the greatest number of affected genes involved in neuronal functions, two implicated in peroxisomal biogenesis, and some others related to telomere protection and DNA repair. The child had a mixture of very short and normal length telomeres, a condition commonly observed in the elderly and in individuals with chronic degenerative diseases.
Conclusion: The abnormal function of peroxisomes and altered gene expression found in the patient under study could explain the affected telomere length. Further studies are needed to explore this possibility.
Keywords: D-bifunctional protein deficiency, gene expression, telomere length, peroxisomes