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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Molecular and clinical analysis of ALPL in a cohort of patients with suspicion of Hypophosphatasia
American Journal of Medical Genetics, Part A, Volume 173, No. 3, Year 2017
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Description
Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.
Authors & Co-Authors
Tenorio, Jair
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Álvarez, Ignacio
Spain, Madrid
Alexion Pharmaceuticals
Riancho-Zarrabeitia, Leyre
Spain, Santander
Hospital Universitario Marqués de Valdecilla
Martos-Moreno, Gabriel
Spain, Madrid
Hospital Infantil Universitario Niño Jesús
Spain, Madrid
Universidad Autónoma de Madrid
Spain, Madrid
Instituto de Salud Carlos Iii
Mandrile, Giorgia
Italy, Orbassano
Azienda Ospedaliero-universitaria San Luigi Gonzaga
Italy, Turin
Università Degli Studi Di Torino, Scuola Di Medicina
de la Flor Crespo, Monserrat
Spain, Madrid
Hospital la Moraleja
Sukchev, Mikhail
Russian Federation, Moscow
Diagnostic Specialist
Sherif, Mostafa
United Arab Emirates
Medical Division
Kramer, Iza
Unknown Affiliation
Darnaude-Ortiz, María T.
Spain, Mostoles
Hospital Universitario de Móstoles
Arias, Pedro
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Gordo, Gema
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Dapía, Irene
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Martinez-Villanueva, Julián
Spain, Madrid
Hospital Infantil Universitario Niño Jesús
Gómez-Rioja, Rubén
Spain, Madrid
Hospital Universitario la Paz
Iturzaeta, Jose Manuel
Spain, Madrid
Hospital Universitario la Paz
Otaify, Ghada A.
Egypt, Giza
National Research Centre
Unzueta, María Teresa García
Spain, Santander
Hospital Universitario Marqués de Valdecilla
Rubinacci, Alessandro
Italy, Milan
Irccs Ospedale San Raffaele
Riancho, José Antonio
Spain, Santander
Hospital Universitario Marqués de Valdecilla
Aglan, Mona Sabry
Egypt, Giza
National Research Centre
Temtamy, Samia Ali Li
Egypt, Giza
National Research Centre
Abdel-Hamid, M. S.
Egypt, Giza
National Research Centre
Argente, Jesús
Spain, Madrid
Hospital Infantil Universitario Niño Jesús
Spain, Madrid
Universidad Autónoma de Madrid
Spain, Madrid
Instituto de Salud Carlos Iii
Ruiz-Perez, Victor L.
Spain, Madrid
Instituto de Salud Carlos Iii
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Heath, Karen E.
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Lapunzina-Badía, Pablo Daniel
Spain, Madrid
Hospital Universitario la Paz
Spain, Madrid
Instituto de Salud Carlos Iii
Statistics
Citations: 36
Authors: 27
Affiliations: 15
Identifiers
Doi:
10.1002/ajmg.a.37991
ISSN:
15524825
e-ISSN:
15524833
Research Areas
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases
Study Design
Cohort Study