Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation
Background/Objectives: X-linked hypophosphataemic rickets (XLH) represents the most frequent type of rickets from genetic origin, it is caused by mutations on the <i>PHEX</i> gene. The main clinical manifestations are short stature and bone deformities. Phenotype variation is observed at...
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2025-01-01
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| author | Marco A. Olivas-Valdez Armando Blanco-López Daniela Velázquez-Arestegui Teresita Vera-Zazueta Douglas Colmenares-Bonilla Lilian Reyes-Morales Miguel A. Blanco-Uriarte Lucero Monterde-Cruz Alberto Hidalgo-Bravo |
| author_facet | Marco A. Olivas-Valdez Armando Blanco-López Daniela Velázquez-Arestegui Teresita Vera-Zazueta Douglas Colmenares-Bonilla Lilian Reyes-Morales Miguel A. Blanco-Uriarte Lucero Monterde-Cruz Alberto Hidalgo-Bravo |
| author_sort | Marco A. Olivas-Valdez |
| collection | DOAJ |
| description | Background/Objectives: X-linked hypophosphataemic rickets (XLH) represents the most frequent type of rickets from genetic origin, it is caused by mutations on the <i>PHEX</i> gene. The main clinical manifestations are short stature and bone deformities. Phenotype variation is observed at the intrafamily and interfamily level. The bases for this variation are not fully understood. The aim of this study was to investigate if there is a phenotype–genotype correlation in a cohort of patients with confirmed diagnosis of XLH. Methods: We recruited a total of 130 patients of Mexican Mestizo origin with confirmed molecular diagnosis of XLH; this is one of the largest cohorts reported. Results: Radiographies for calculating the rickets severity score (RSS) were available from 50 patients. A total of 56 different pathogenic variants were found among the study population; from them, 31 variants have not been previously reported. We compared the RSS values between individuals considering clinical and biochemical characteristics such as age, height, sex, phosphorus, and alkaline phosphatase in serum; no significant differences were observed. Then, we compared the RSS considering if the variant was intronic or exonic and considering the presence of a truncated protein or not. None of the two comparisons showed significant differences. Conclusions: We did not find a genotype–phenotype correlation in the study population. Despite the knowledge regarding the genetic cause of XLH, the mechanisms driving the intrafamily and interfamily variability remain elusive. More analyses looking for the genotype–phenotype correlation are necessary in other populations, especially considering the discovery of new mutations in patients from different origin. |
| format | Article |
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| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-1c5882d5c4944d0ca2ab33d06ff95a512025-01-10T13:16:41ZengMDPI AGDiagnostics2075-44182025-01-011519110.3390/diagnostics15010091Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype CorrelationMarco A. Olivas-Valdez0Armando Blanco-López1Daniela Velázquez-Arestegui2Teresita Vera-Zazueta3Douglas Colmenares-Bonilla4Lilian Reyes-Morales5Miguel A. Blanco-Uriarte6Lucero Monterde-Cruz7Alberto Hidalgo-Bravo8Clínica Shriners Tijuana, Av. Paseo de Los Héroes 10999, Zona Río, Zona Urbana Rio Tijuana, Tijuana 22010, MexicoHospital Shriners para Niños-México, Av. del Imán #257, Pedregal de Sta. Úrsula, Coyoacán, Ciudad de México 04600, MexicoHospital Shriners para Niños-México, Av. del Imán #257, Pedregal de Sta. Úrsula, Coyoacán, Ciudad de México 04600, MexicoHospital Ángeles Tijuana, Av. Paseo de Los Héroes 10999, Zona Río, Zona Urbana Rio Tijuana, Tijuana 22010, MexicoServicio de Ortopedia Pediátrica, Hospital Regional de Alta Especialidad del Bajío, Blvd. Milenio 130, Col San Carlos la Roncha, León 37544, MexicoDepartamento de Nefrología, Instituto Nacional de Pediatría, Av. Insurgentes Sur 3700 Letra C, Insurgentes Cuicuilco, Ciudad de México 04530, MexicoHospital Shriners para Niños-México, Av. del Imán #257, Pedregal de Sta. Úrsula, Coyoacán, Ciudad de México 04600, MexicoStar Medica-Hospital Infantil Privado, Nueva York 15, Col. Nápoles, Ciudad de México 03810, MexicoDepartamento de Medicina Genómica, Instituto Nacional de Rehabilitación, Calzada México-Xochimilco 289, Col. Arenal de Guadalupe, Ciudad de México 14389, MexicoBackground/Objectives: X-linked hypophosphataemic rickets (XLH) represents the most frequent type of rickets from genetic origin, it is caused by mutations on the <i>PHEX</i> gene. The main clinical manifestations are short stature and bone deformities. Phenotype variation is observed at the intrafamily and interfamily level. The bases for this variation are not fully understood. The aim of this study was to investigate if there is a phenotype–genotype correlation in a cohort of patients with confirmed diagnosis of XLH. Methods: We recruited a total of 130 patients of Mexican Mestizo origin with confirmed molecular diagnosis of XLH; this is one of the largest cohorts reported. Results: Radiographies for calculating the rickets severity score (RSS) were available from 50 patients. A total of 56 different pathogenic variants were found among the study population; from them, 31 variants have not been previously reported. We compared the RSS values between individuals considering clinical and biochemical characteristics such as age, height, sex, phosphorus, and alkaline phosphatase in serum; no significant differences were observed. Then, we compared the RSS considering if the variant was intronic or exonic and considering the presence of a truncated protein or not. None of the two comparisons showed significant differences. Conclusions: We did not find a genotype–phenotype correlation in the study population. Despite the knowledge regarding the genetic cause of XLH, the mechanisms driving the intrafamily and interfamily variability remain elusive. More analyses looking for the genotype–phenotype correlation are necessary in other populations, especially considering the discovery of new mutations in patients from different origin.https://www.mdpi.com/2075-4418/15/1/91X-Linked hypophosphatemic rickets<i>PHEX</i>genotype–phenotype correlationboneXLH |
| spellingShingle | Marco A. Olivas-Valdez Armando Blanco-López Daniela Velázquez-Arestegui Teresita Vera-Zazueta Douglas Colmenares-Bonilla Lilian Reyes-Morales Miguel A. Blanco-Uriarte Lucero Monterde-Cruz Alberto Hidalgo-Bravo Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation Diagnostics X-Linked hypophosphatemic rickets <i>PHEX</i> genotype–phenotype correlation bone XLH |
| title | Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation |
| title_full | Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation |
| title_fullStr | Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation |
| title_full_unstemmed | Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation |
| title_short | Clinical, Radiographic, and Molecular Analysis of Patients with X-Linked Hypophosphatemic Rickets: Looking for Phenotype–Genotype Correlation |
| title_sort | clinical radiographic and molecular analysis of patients with x linked hypophosphatemic rickets looking for phenotype genotype correlation |
| topic | X-Linked hypophosphatemic rickets <i>PHEX</i> genotype–phenotype correlation bone XLH |
| url | https://www.mdpi.com/2075-4418/15/1/91 |
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