@misc{10481/57335,
year = {2019},
month = {7},
url = {http://hdl.handle.net/10481/57335},
abstract = {Hypophosphatasia (HPP) is a genetic disease caused by one or several mutations in ALPL gene
encoding the tissue-nonspecific alkaline phosphatase affecting the mineralization process. Due to
its low prevalence and lack of recognition, this metabolic disorder is generally confused with other
more frequent bone disorders. An assessment of serum total alkaline phosphatase (ALP) levels
was performed in 78,590 subjects. Pyridoxal-5′-phosphate (PLP) concentrations were determined
and ALPL gene was sequenced in patients potentially affected by HPP. Functional validation of the
novel mutations found was performed using a cell-based assay. Our results showed persistently low
serum ALP levels in 0.12% of subjects. Among the studied subjects, 40% presented with HPP-related
symptoms. Nine of them (~28%) had a history of fractures, 5 (~16%) subjects showed chondrocalcinosis
and 4 (~13%) subjects presented with dental abnormalities. Eleven subjects showed increased PLP
concentrations. Seven of them showed ALPL gene mutations (2 of the mutations corresponded to novel
genetic variants). In summary, we identified two novel ALPL gene mutations associated with adult
HPP. Using this protocol, almost half of the studied patients were diagnosed with HPP. Based on these
results, the estimated prevalence of mild HPP in Spain could be up to double than previously reported.},
organization = {Resource for Biocomputing, Visualization,
and Informatics at the University of California, San Francisco (with support from NIH P41-GM103311)},
organization = {grants from Alexion and FEIOMM,
by Instituto de Salud Carlos III (grants PI18-00803 and PI18-01235)},
organization = {co-funding from FEDER and by Junta
de Andalucía (grant PI-0207-2016)},
organization = {GM-N is supported by the predoctoral program from Instituto de Salud
Carlos III (FI17/00178) and by the Research Initiation Grants for Official Master Students program from the
University of Granada (2017)},
organization = {PJR is a Ramon y Cajal Researcher from the MINECO (RYC-2015-18383) at
GENyO and University of Granada.},
publisher = {Scientific Reports},
title = {Epidemiological, Clinical and Genetic Study of Hypophosphatasia in A Spanish Population: Identification of Two Novel Mutations in The Alpl Gene},
doi = {10.1038/s41598-019-46004-2},
author = {García Fontana, Cristina and Villa Suárez, Juan M. and Andujar Vera, Francisco and González Salvatierra, Sheila and Martínez Navajas, Gonzalo and Real, Pedro J. and Gómez Vida, José María and de Haro, Tomas and García Fontana, Beatriz and Muñoz Torres, Manuel Eduardo},
}