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Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3

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 patient...

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Autores principales: Acar, Sezer, BinEssa, Huda A., Demir, Korcan, Al-Rijjal, Roua A., Zou, Minjing, Çatli, Gönül, Anık, Ahmet, Al-Enezi, Anwar F., Özışık, Seçil, Al-Faham, Manar S. A., Abacı, Ayhan, Dündar, Bumin, Kattan, Walaa E., Alsagob, Maysoon, Kavukçu, Salih, Tamimi, Hamdi E., Meyer, Brian F., Böber, Ece, Shi, Yufei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837132/
https://www.ncbi.nlm.nih.gov/pubmed/29505567
http://dx.doi.org/10.1371/journal.pone.0193388
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author Acar, Sezer
BinEssa, Huda A.
Demir, Korcan
Al-Rijjal, Roua A.
Zou, Minjing
Çatli, Gönül
Anık, Ahmet
Al-Enezi, Anwar F.
Özışık, Seçil
Al-Faham, Manar S. A.
Abacı, Ayhan
Dündar, Bumin
Kattan, Walaa E.
Alsagob, Maysoon
Kavukçu, Salih
Tamimi, Hamdi E.
Meyer, Brian F.
Böber, Ece
Shi, Yufei
author_facet Acar, Sezer
BinEssa, Huda A.
Demir, Korcan
Al-Rijjal, Roua A.
Zou, Minjing
Çatli, Gönül
Anık, Ahmet
Al-Enezi, Anwar F.
Özışık, Seçil
Al-Faham, Manar S. A.
Abacı, Ayhan
Dündar, Bumin
Kattan, Walaa E.
Alsagob, Maysoon
Kavukçu, Salih
Tamimi, Hamdi E.
Meyer, Brian F.
Böber, Ece
Shi, Yufei
author_sort Acar, Sezer
collection PubMed
description 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.
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spelling pubmed-58371322018-03-19 Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3 Acar, Sezer BinEssa, Huda A. Demir, Korcan Al-Rijjal, Roua A. Zou, Minjing Çatli, Gönül Anık, Ahmet Al-Enezi, Anwar F. Özışık, Seçil Al-Faham, Manar S. A. Abacı, Ayhan Dündar, Bumin Kattan, Walaa E. Alsagob, Maysoon Kavukçu, Salih Tamimi, Hamdi E. Meyer, Brian F. Böber, Ece Shi, Yufei PLoS One Research Article 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. Public Library of Science 2018-03-05 /pmc/articles/PMC5837132/ /pubmed/29505567 http://dx.doi.org/10.1371/journal.pone.0193388 Text en © 2018 Acar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Acar, Sezer
BinEssa, Huda A.
Demir, Korcan
Al-Rijjal, Roua A.
Zou, Minjing
Çatli, Gönül
Anık, Ahmet
Al-Enezi, Anwar F.
Özışık, Seçil
Al-Faham, Manar S. A.
Abacı, Ayhan
Dündar, Bumin
Kattan, Walaa E.
Alsagob, Maysoon
Kavukçu, Salih
Tamimi, Hamdi E.
Meyer, Brian F.
Böber, Ece
Shi, Yufei
Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title_full Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title_fullStr Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title_full_unstemmed Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title_short Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3
title_sort clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: novel mutations in phex and slc34a3
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837132/
https://www.ncbi.nlm.nih.gov/pubmed/29505567
http://dx.doi.org/10.1371/journal.pone.0193388
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