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- Pelletier, F., et al.
(författare)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Bond, A. E., et al.
(författare)
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Development of approaches for modelling coupled thermal–hydraulic–mechanical–chemical processes in single granite fracture experiments
- 2016
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Ingår i: Environmental Earth Sciences. - : Springer. - 1866-6280 .- 1866-6299. ; 75:19
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Tidskriftsartikel (refereegranskat)abstract
- The geological formation immediately surrounding a nuclear waste disposal facility has the potential to undergo a complex set of physical and chemical processes starting from construction and continuing many years after closure. The DECOVALEX project (DEvelopment of COupled models and their VALidation against EXperiments) was established and maintained by a variety of waste management organizations, regulators and research organizations to help improve capabilities in experimental interpretation, numerical modelling and blind prediction of complex coupled systems. In the present round of DECOVALEX (D-2015), one component of Task C1 has considered the detailed experimental work of Yasuhara et al. (Appl Geochem 26:2074–2088, 2011), wherein three natural fractures in Mizunami granite are subject to variable fluid flows, mechanical confining pressure and different applied temperatures. This paper presents a synthesis of the completed work of six separate research teams, building on work considering a single synthetic fracture in novaculite. A range of approaches are presented including full geochemical reactive transport modelling and 2D and 3D high-resolution coupled thermo–hydro–mechanical–chemical (THMC) models. The work shows that reasonable fits can be obtained to the experimental data using a variety of approaches, but considerable uncertainty remains as to the relative importance of competing process sets. The work also illustrates that a good understanding of fracture topography, interaction with the granite matrix, a good understanding of the geochemistry and the associated multi-scale THMC process behaviours is a necessary pre-cursor to considering predictive models of such a system.
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