A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype
AimX-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype–phenotype correlation...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1215952/full |
| _version_ | 1797680752247177216 |
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| author | Mauro Borghi Mauro Borghi Leopoldo Muniz da Silva Luciana Bispo Carlos A. Longui |
| author_facet | Mauro Borghi Mauro Borghi Leopoldo Muniz da Silva Luciana Bispo Carlos A. Longui |
| author_sort | Mauro Borghi |
| collection | DOAJ |
| description | AimX-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype–phenotype correlation in a cohort of XLH patients.MethodsThis is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study.ResultsA total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%.ConclusionsOur analysis did not identify any specific genotype as a predictor. No significant genotype–phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment. |
| first_indexed | 2024-03-11T23:34:40Z |
| format | Article |
| id | doaj.art-421e5d5960414bf3adf09b9035e63c35 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-03-11T23:34:40Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-421e5d5960414bf3adf09b9035e63c352023-09-20T04:34:37ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-09-011110.3389/fped.2023.12159521215952A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotypeMauro Borghi0Mauro Borghi1Leopoldo Muniz da Silva2Luciana Bispo3Carlos A. Longui4School of Medical Sciences Santa Casa SP and Pediatric Endocrinology Unit, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, BrazilHospital São Luiz—Rede D´Or—CMA, Departament of Anesthesiology, São Paulo, BrazilHospital São Luiz—Rede D´Or—CMA, Departament of Anesthesiology, São Paulo, BrazilLaboratório Mendelics, Department of Genetic, São Paulo, BrazilSchool of Medical Sciences Santa Casa SP and Pediatric Endocrinology Unit, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, BrazilAimX-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype–phenotype correlation in a cohort of XLH patients.MethodsThis is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study.ResultsA total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%.ConclusionsOur analysis did not identify any specific genotype as a predictor. No significant genotype–phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment.https://www.frontiersin.org/articles/10.3389/fped.2023.1215952/fullgenotypegenotype–phenotype correlationphosphatevariantsX-linked hypophosphatemic ricketsphenotype |
| spellingShingle | Mauro Borghi Mauro Borghi Leopoldo Muniz da Silva Luciana Bispo Carlos A. Longui A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype Frontiers in Pediatrics genotype genotype–phenotype correlation phosphate variants X-linked hypophosphatemic rickets phenotype |
| title | A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype |
| title_full | A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype |
| title_fullStr | A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype |
| title_full_unstemmed | A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype |
| title_short | A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype |
| title_sort | genetic study of a brazilian cohort of patients with x linked hypophosphatemia reveals no correlation between genotype and phenotype |
| topic | genotype genotype–phenotype correlation phosphate variants X-linked hypophosphatemic rickets phenotype |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1215952/full |
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