A rapid screening of a recurrent CYP24A1 pathogenic variant opens the way to molecular testing for Idiopathic Infantile Hypercalcemia (IIH)
| Autor: | Ettore Capoluongo, Jacopo Gervasoni, Daniele Cappellani, Giovanni Luca Scaglione, Aniello Primiano, Elisa De Paolis, Giovanni Gambaro, Angelo Minucci, Pietro Manuel Ferraro, Claudio Marcocci, Maria De Bonis |
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| Přispěvatelé: | De Paolis, E., Minucci, A., De Bonis, M., Scaglione, G. L., Gervasoni, J., Primiano, A., Ferraro, P. M., Cappellani, D., Marcocci, C., Gambaro, G., Capoluongo, Ettore Domenico |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry 030232 urology & nephrology Parathyroid hormone Bioinformatics Biochemistry Gastroenterology Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA 0302 clinical medicine Medicine Transition Temperature Hypercalciuria Infantile hypercalcemia Vitamin D Vitamin D3 24-Hydroxylase General Medicine Nephrocalcinosis Molecular Diagnostic Techniques Mutation (genetic algorithm) Human medicine.medical_specialty High resolution melting analysis Genotype Urology Molecular Diagnostic Technique MEDLINE High Resolution Melt Melting curve analysis 03 medical and health sciences Kidney Calculi Text mining CYP24A1 Internal medicine Humans Hypercalcemia Idiopathic Infantile Hypercalcemia Nephrocalcinosi Genetic Variation Biochemistry (medical) business.industry Molecular diagnostics medicine.disease High resolution melting analysi 030104 developmental biology Kidney stone disease Mutation business |
| Popis: | Introduction Loss-of-function mutations in cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia (IIH) and adult kidney stone disease. The enzyme deficiency leads to an impaired vitamin D catabolism pathway, resulting in a syndrome characterized by recurrent hypercalcemia, hypercalciuria and suppressed parathyroid hormone (PTH) levels. In these patients, the genetic evaluation of CYP24A1 is an important diagnostic tool, allowing the definitive diagnosis of IIH. Methods A rapid CYP24A1 gene testing based on High Resolution Melting Analysis (HRMA) was designed in order to detect the CYP24A1 c.428_430delAAG (p.Glu143del), a recurrent IIH-associated variant. Results HRMA method was able to identify c.428_430delAAG genotypes evaluating melting curve shape and melting temperature (Tm). Heterozygous samples exhibited a typical melting profile while homozygous samples showed a specific Tm shift. Conclusions We provide evidence about application of HRMA in unambiguous genotyping of the CYP24A1 c.428_430delAAG variant, making this method useful in clinical molecular diagnostics. This approach opens the way to a helpful molecular analysis of CYP24A1 gene in IIH diagnosis, to an improved pharmacological treatment strategy and to a reduced risk of recurrent stones and worsening nephrocalcinosis. |
| Databáze: | OpenAIRE |
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