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- Wiessner, M., et al.
(författare)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Tidskriftsartikel (refereegranskat)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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| 5. |
- Chenot, E., et al.
(författare)
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Diagenetic and detrital influences on clay mineralogy and carbon isotope geochemistry of Campanian-Maastrichtian sediments in the Tremp-Graus Basin (southern Pyrenees, Spain) : [Influencias diagenéticas y detríticas en la mineralogía de las arcillas y en la geoquímica de los isótopos de carbono de los sedimentos del Campaniano-Maastrichtiano de la cuenca de Tremp-Graus (sur de los Pirineos, España)]
- 2022
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Ingår i: Journal of Iberian Geology. - : Springer Science and Business Media LLC. - 1698-6180 .- 1886-7995. ; 48:1, s. 29-43
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Tidskriftsartikel (refereegranskat)abstract
- A 1000 m-thick sequence of Upper Cretaceous sediments outcropping in the Isabena Valley (Tremp-Graus Basin, Spain) has been studied to explore the evolution of environmental conditions that prevailed in this basin. A biostratigraphic study based on calcareous nannofossils was carried out to better constraint the age of the deposits, supplemented by carbon isotope stratigraphy on bulk carbonates. Clay mineral assemblages were identified by X-Ray diffraction combined with organic matter (OM) characterisation by Rock–Eval pyrolysis. The Late Campanian Event and Campanian Maastrichtian Boundary Event are clearly identified from the new δ13Ccarb dataset. The clay assemblage is composed of a complex mixture of chlorite, illite, kaolinite and mixed-layers including illite–smectite and chlorite–smectite. A progressive illitisation of smectite is recorded from the top to the base of the section due to the increasing burial depth. This evolution is consistent with increasing Tmax values of OM evolving from 425 (immature OM) to 449 °C (mature OM) from the top to the base of the section. Thus, detrital minerals are preserved only in the upper part of the section. The clay sedimentation is dominated by smectites likely originating from the Ebro massif, while increasing proportions of kaolinite are recorded from the uppermost Campanian and during the Maastrichtian. This evolution of the clay mineral assemblage is interpreted as a result from a change of source from south to northeast, with contributions from kaolinite-rich weathering profiles (including bauxites) to the northeast of the study area, reflecting a more hydrolysing climate.
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- Wang, CH, et al.
(författare)
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Consensus statement on standard of care for congenital muscular dystrophies
- 2010
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Ingår i: Journal of child neurology. - : SAGE Publications. - 1708-8283 .- 0883-0738. ; 25:12, s. 1559-1581
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Tidskriftsartikel (refereegranskat)abstract
- Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee.
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