Clinical characteristics of adrenoleukodystrophy with a novel ABCD1 gene mutation / 中华内分泌代谢杂志

Objective:To analyze the clinical features and genetic background of adrenoleukodystrophy(ALD).Methods:In this study, we reported a rare case of ALD who initially presented with progressive bilateral lower limb weakness. The clinical data of the patient and his family members were collected and the ABCD1 gene was sequenced for the patient and his three daughters by a high-throughput sequencing method.Results:The proband had a later onset of symptoms, a prolonged course of the disease, and initially exhibited bilateral lower limb weakness and nocturnal muscle spasms. The disease progressed to spastic quadriplegia, aphasia, dementia, swallowing difficulties, and urinary and fecal incontinence. Serum very-long-chain fatty acid concentrations were elevated. Subclinical cortisol secretion abnormalities were observed. Cranial imaging indicated symmetrical reduction in density around the lateral ventricles and white matter degeneration. The proband′s ABCD1 gene analysis revealed a novel heterozygous mutation c. 1367G>A, p. R456H. His three daughters carried the same nucleotide heterozygous mutation.Conclusion:This study investigates the clinical characteristics of ALD, providing additional clinical evidence for the diagnosis and treatment of this condition. Additionally, a novel mutation in the ABCD1 gene was identified, contributing to the genetic variation database.

Phosphorylation regulates cullin-based ubiquitination in tumorigenesis

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.