84 research outputs found

    Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.

    Get PDF
    CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder

    Fuorescent retrograde neuronal labeling in rat by means of substances binding specifically to adenine-thymine rich DNA

    No full text
    Six fluorescent substances, binding specifically to adenine-thymine rich DNA, were injected in rat caudate-putamen. This resulted in retrograde axonal transport and fluorescent retrograde labeling of neurons in center-medium parafascicular nucleus, substantia nigra and dorsal raphe. Two of these substances, i.e. "True Blue' and 'Granular Blue', give a very striking blue fluorescent retrograde neuronal labeling. Mid-thoracic spinal injections of these two substances in rat also resulted in a pronounced retrograde fluorescent labeling of neurons of the descending brainstem pathways and of neurons in the sensori-motor cortex

    Retrograde transport of bisbenzimide and propidium iodide through axons to their parent cell bodies

    No full text
    Two fluorescent substances bisbenzimide (Bb), which fluoresces yellow-green and propidium iodide (PI), which fluoresces orange were found to be transported retrogradely through axons to their parent cell bodies in rat and cat. Bb gives a very strong and long lasting fluorescent retrograde neuronal labeling and is very effectively transported over long distances both in rat and cat. Bb and PI also label glial nuclei around retrogradely labeled neurons. Bb in addition labels glial nuclei along axons through which it is transported. Bb and PI can be transported retrogradely through two divergent collaterals to one and the same cell
    corecore