ArticleMolecular genetics and metabolism2015
Molecular diagnosis of hypophosphatasia and differential diagnosis by targeted Next Generation Sequencing.
Article in Molecular genetics and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review.Journal of inherited metabolic disease · 2025Pooled it
- Hypophosphatasia: Results of a Country-Wide Selective Screening Program Using NGS Technology as a First-Tier Test.International journal of molecular sciences · 2026Article
- Review
- Evaluating variants of uncertain significance in adult zebrafish via prime editing: a proof of concept with a COL1A2 variant.BMC medical genomics · 2025Article
- Revisiting the Genetics of Hypophosphatasia.Journal of inherited metabolic disease · 2025Review
- Adult-onset hypophosphatasia diagnosed after consecutive tooth loss during orthodontic treatment: a case report.Journal of medical case reports · 2024Article
- Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider-Retrospective Analyses over Fifteen Years.Journal of clinical medicine · 2024Article
- The Benefits of Whole-Exome Sequencing in the Differential Diagnosis of Hypophosphatasia.International journal of molecular sciences · 2024Article
- Whole genome sequencing in adults with clinical hallmarks of hypophosphatasia negative for ALPL variants.Molecular biology reports · 2024Observational
- A Delphi panel to build consensus on assessing disease severity and disease progression in adult patients with hypophosphatasia in the United States.Journal of endocrinological investigation · 2024Article
- Article
- Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024Review
- Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia.Osteoporosis and sarcopenia · 2023Review
- Article
- Article
- Childhood Hypophosphatasia Associated with a Novel BiallelicInternational journal of molecular sciences · 2022Article
- Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome.Current issues in molecular biology · 2022Article
- Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?Frontiers in dental medicine · 2022Article
- Hypophosphatasia.Journal of clinical medicine · 2021Review
- Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark.Bone reports · 2021Article
Corrections and comments
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Authors and funding
26 authors at 17 institutions in 2 countries.
Funding
Abstract
Hypophosphatasia (HPP) is a rare inherited skeletal dysplasia due to loss of function mutations in the ALPL gene. The disease is subject to an extremely high clinical heterogeneity ranging from a perinatal lethal form to odontohypophosphatasia affecting only teeth. Up to now genetic diagnosis of HPP is performed by sequencing the ALPL gene by Sanger methodology. Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL mutations, OI and CD genes had often to be analyzed, lengthening the time before diagnosis. We report here our 18-month experience in testing 46 patients for HPP and differential diagnosis by targeted NGS and show that this strategy is efficient and useful. We used an array including ALPL gene, genes of differential diagnosis COL1A1 and COL1A2 that represent 90% of OI cases, SOX9, responsible for CD, and 8 potentially modifier genes of HPP. Seventeen patients were found to carry a mutation in one of these genes. Among them, only 10 out of 15 cases referred for HPP carried a mutation in ALPL and 5 carried a mutation in COL1A1 or COL1A2. Interestingly, three of these patients were adults with fractures and/or low BMD. Our results indicate that HPP and OI may be easily misdiagnosed in the prenatal stage but also in adults with mild symptoms for these diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.