RT Journal Article
T1 Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia.
A1 Sanabria-de la Torre, Raquel
A1 Martinez-Heredia, Luis
A1 Gonzalez-Salvatierra, Sheila
A1 Andujar-Vera, Francisco
A1 Iglesias-Baena, Ivan
A1 Villa-Suarez, Juan Miguel
A1 Contreras-Bolivar, Victoria
A1 Corbacho-Soto, Mario
A1 Martinez-Navajas, Gonzalo
A1 Real, Pedro J
A1 Garcia-Fontana, Cristina
A1 Muñoz-Torres, Manuel
A1 Garcia-Fontana, Beatriz
K1 alkaline phosphatase
K1 bone
K1 enzymatic activity
K1 genetic variant
K1 hypophosphatasia
K1 mineralization
K1 pyridoxal 5´ phosphate
AB Hypophosphatasia (HPP) a rare disease caused by mutations in the ALPL gene encoding for the tissue-nonspecific alkaline phosphatase protein (TNSALP), has been identified as a potentially under-diagnosed condition worldwide which may have higher prevalence than currently established. This is largely due to the overlapping of its symptomatology with that of other more frequent pathologies. Although HPP is usually associated with deficient bone mineralization, the high genetic variability of ALPL results in high clinical heterogeneity, which makes it difficult to establish a specific HPP symptomatology. In the present study, three variants of ALPL gene with uncertain significance and no previously described (p.Del Glu23_Lys24, p.Pro292Leu and p.His379Asn) were identified in heterozygosis in patients diagnosed with HPP. These variants were characterized at phenotypic, functional and structural levels. All genetic variants showed significantly lower in vitro ALP activity than the wild-type (WT) genotype (p-value
PB Frontiers Research Foundation
SN 1664-2392
YR 2022
FD 2022-03-14
LK http://hdl.handle.net/10668/20562
UL http://hdl.handle.net/10668/20562
LA en
NO Sanabria-de la Torre R, Martínez-Heredia L, González-Salvatierra S, Andújar-Vera F, Iglesias-Baena I, Villa-Suárez JM, et al. Characterization of Genetic Variants of Uncertain Significance for the ALPL Gene in Patients With Adult Hypophosphatasia. Front Endocrinol (Lausanne). 2022 Apr 14;13:863940.
NO This research was funded by the Instituto de Salud Carlos III grants (PI18-00803, PI21/01069 and PI18-01235), co-funded by the European Regional Development Fund (FEDER) and by Junta de Andalucía grant (PI-0268-2019). In addition, VC-B is supported by postdoctoral fellowship from Junta de Andalucía (RH-0141-2020) and JMV-S and SG-S are funded by predoctoral fellowships from Instituto de Salud Carlos III (CM19/00188 and FI19/00118 respectively). CG-F and RS-dT are funded by postdoctoral Sara Borrell fellowship and Research investigator grant in the framework of the youth guarantee Program from the Instituto de Salud Carlos III and the University of Granada with co-funding by FEDER respectively (CD20/00022 and 8110 grant number). GM-N is supported by the predoctoral program from Instituto de Salud Carlos III (FI17/00178) and PR is a Ramon y Cajal Researcher from the MINECO (RYC-2015-18383) at GENyO and University of Granada. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
DS RISalud
RD Apr 10, 2025