Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
| Autor: | Bumin Dündar, Ayhan Abaci, Ece Böber, Secil Ozisik, Gönül Çatlı, Yufei Shi, Maysoon Alsagob, Minjing Zou, Huda A BinEssa, Brian F. Meyer, Roua A. Al-Rijjal, Sezer Acar, Salih Kavukçu, Korcan Demir, Walaa E Kattan, Anwar F Al-Enezi, Ahmet Anık, Hamdi E Tamimi, Manar S A Al-Faham |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Gene Identification and Analysis lcsh:Medicine medicine.disease_cause Compound heterozygosity Database and Informatics Methods Exon 0302 clinical medicine Medicine and Health Sciences Child lcsh:Science Genetics Mutation Multidisciplinary medicine.diagnostic_test biology Nonsense Mutation Genomics Middle Aged Clinical Laboratory Sciences Pedigree Chemistry Clinical Laboratories Deletion Mutation Child Preschool Physical Sciences Female Familial Hypophosphatemic Rickets medicine.symptom Hypophosphatemia Research Article Adult 030209 endocrinology & metabolism Sodium-Phosphate Cotransporter Proteins Type IIc Research and Analysis Methods Genome Complexity Asymptomatic Phosphates 03 medical and health sciences Diagnostic Medicine medicine Humans Mutation Detection Genetic testing Base Sequence business.industry CLCN5 PHEX lcsh:R Chemical Compounds Biology and Life Sciences Computational Biology Human Genetics medicine.disease PHEX Phosphate Regulating Neutral Endopeptidase Introns Fibroblast Growth Factor-23 Biological Databases 030104 developmental biology Mutation Databases biology.protein lcsh:Q business |
| Zdroj: | PLoS ONE, Vol 13, Iss 3, p e0193388 (2018) PLoS ONE |
| Popis: | Background Hereditary hypophosphatemia is a group of rare renal phosphate wasting disorders. The diagnosis is based on clinical, radiological, and biochemical features, and may require genetic testing to be confirmed. Methodology Clinical features and mutation spectrum were investigated in patients with hereditary hypophosphatemia. Genomic DNA of 23 patients from 15 unrelated families were screened sequentially by PCR-sequencing analysis for mutations in the following genes: PHEX, FGF23, DMP1, ENPP1, CLCN5, SLC34A3 and SLC34A1. CytoScan HD Array was used to identify large deletions. Results Genetic evaluation resulted in the identification of an additional asymptomatic but intermittent hypophosphatemic subject. Mutations were detected in 21 patients and an asymptomatic sibling from 13 families (86.6%, 13/15). PHEX mutations were identified in 20 patients from 12 families. Six of them were novel mutations present in 9 patients: c.983_987dupCTACC, c.1586+2T>G, c.1206delA, c.436+1G>T, c.1217G>T, and g.22,215,887-22,395,767del (179880 bp deletion including exon 16-22 and ZNF645). Six previously reported mutations were found in 11 patients. Among 12 different PHEX mutations, 6 were de novo mutations. Patients with de novo PHEX mutations often had delayed diagnosis and significantly shorter in height than those who had inherited PHEX mutations. Novel compound heterozygous mutations in SLC34A3 were found in one patient and his asymptomatic sister: c.1335+2T>A and c.1639_1652del14. No mutation was detected in two families. Conclusions This is the largest familial study on Turkish patients with hereditary hypophosphatemia. PHEX mutations, including various novel and de novo variants, are the most common genetic defect. More attention should be paid to hypophosphatemia by clinicians since some cases remain undiagnosed both during childhood and adulthood. |
| Databáze: | OpenAIRE |
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