Advanced search

Vol 72, No 4 (2021)
Review paper
Published online: 2021-06-25

open access

View PDF Download PDF file
Page views 1737
Article views/downloads 1217
Get Citation

Connect on Social Media

Connect on Social Media

Genetic basis of hereditary hypophosphataemic rickets and phenotype presentation in children and adults

Nahid Tavana1, Karuppiah Thilakavathy12, Marina L. Kennerson345, Tzer Hwu Ting6
DOI: 10.5603/EP.a2021.0062
Pubmed: 34292571
Endokrynol Pol 2021;72(4):366-394.

Abstract

Hypophosphataemic rickets (HR) is a genetic disorder causing defects in the renal handling of phosphorus, resulting in rickets. HR can be classified into two groups. First — those with excess fibroblast growth factor 23 (FGF23) levels, which are due to gene mutations in extrarenal factors and include X-linked dominant hypophosphataemic rickets (XLHR), autosomal dominant hypophosphataemic rickets (ADHR), autosomal recessive hypophosphataemic rickets (ARHR), and hypophosphataemic rickets with hyperparathyroidism. Second — those with normal or low FGF23, which are caused by gene mutations in renal tubular phosphate transporters and include hereditary hypophosphataemic rickets with hypercalciuria (HHRH) and X-linked recessive hypophosphataemic rickets. The radiographical changes and clinical features of rickets in various types of HR are similar but not identical. Short stature, bone deformities mainly in the lower limbs, and dental problems are typical characteristics of HR. Although the initial diagnosis of HR is usually based on physical, radiological, and biochemical features, molecular genetic analysis is important to confirm the diagnosis and differentiate the type of HR. In this review, we describe clinical and biochemical features as well as genetic causes of different types of HR. The clinical and biochemical characteristics presented in this review can help in the diagnosis of different types of HR and, therefore, direct genetic analysis to look for the specific gene mutation.

Keywords: hypophosphatemiahypophosphataemic ricketsphenotypePHEXFGF23clinical featuresmutationXLHR

Article available in PDF format

View PDF Download PDF file

References

  1. Lambert AS, Linglart A. Hypocalcaemic and hypophosphatemic rickets. Best Pract Res Clin Endocrinol Metab. 2018; 32(4): 455–476.
    CrossRefPubMed
  2. Razali NN, Hwu TT, Thilakavathy K. Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets. J Pediatr Endocrinol Metab. 2015; 28(9-10): 1009–1017.
    CrossRefPubMed
  3. Jagtap VS, Sarathi V, Lila AR, et al. Hypophosphatemic rickets. Indian J Endocrinol Metab. 2012; 16(2): 177–182.
    CrossRefPubMed
  4. Angham A-M AM, Rajaa A. Types of Rickets. Ann Orthop Rheumatol. 2017; 5: 1085.
  5. Albright F. Rickets resistant to vitamin D therapy. Arch Ped Adolesc Med. 1937; 54(3): 529.
    CrossRef
  6. Lin X, Zhu Y, Luo J, et al. Genetic analysis of three families with X-linked dominant hypophosphatemic rickets. J Pediatr Endocrinol Metab. 2018; 31(7): 789–797.
    CrossRefPubMed
  7. Acar S, Demir K, Shi Y. Genetic Causes of Rickets. J Clin Res Pediatr Endocrinol. 2017; 9(Suppl 2): 88–105.
    CrossRefPubMed
  8. Bitzan M, Goodyer PR. Hypophosphatemic Rickets. Pediatr Clin North Am. 2019; 66(1): 179–207.
    CrossRefPubMed
  9. Pavone V, Testa G, Gioitta Iachino S, et al. Hypophosphatemic rickets: etiology, clinical features and treatment. Eur J Orthop Surg Traumatol. 2015; 25(2): 221–226.
    CrossRefPubMed
  10. Robinson ME, AlQuorain H, Murshed M, et al. Mineralized tissues in hypophosphatemic rickets. Pediatr Nephrol. 2020; 35(10): 1843–1854.
    CrossRefPubMed
  11. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet. 1995; 11(2): 130–136.
    CrossRefPubMed
  12. Guven A, Al-Rijjal RA, BinEssa HA, et al. Mutational analysis of PHEX, FGF23 and CLCN5 in patients with hypophosphataemic rickets. Clin Endocrinol (Oxf). 2017; 87(1): 103–112.
    CrossRefPubMed
  13. Ruppe MD, Brosnan PG, Au KS, et al. Mutational analysis of PHEX, FGF23 and DMP1 in a cohort of patients with hypophosphatemic rickets. Clin Endocrinol (Oxf). 2011; 74(3): 312–318.
    CrossRefPubMed
  14. Filisetti D, Ostermann G, von Bredow M, et al. Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues. Eur J Hum Genet. 1999; 7(5): 615–619.
    CrossRefPubMed
  15. Vakharia JD, Matlock K, Taylor HO, et al. Craniosynostosis as the Presenting Feature of X-linked Hypophosphatemic Rickets. Pediatrics. 2018; 141(Suppl 5): S515–S519.
    CrossRefPubMed
  16. Carpenter TO, Imel EA, Holm IA, et al. A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res. 2011; 26(7): 1381–1388.
    CrossRefPubMed
  17. Holm IA, Nelson AE, Robinson BG, et al. Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2001; 86(8): 3889–3899.
    CrossRefPubMed
  18. Christov M, Jüppner H. Phosphate homeostasis disorders. Best Pract Res Clin Endocrinol Metab. 2018; 32(5): 685–706.
    CrossRefPubMed
  19. Christie PT, Harding B, Nesbit MA, et al. X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene. J Clin Endocrinol Metab. 2001; 86(8): 3840–3844.
    CrossRefPubMed
  20. Cho HY, Lee BH, Kang JuH, et al. A clinical and molecular genetic study of hypophosphatemic rickets in children. Pediatr Res. 2005; 58(2): 329–333.
    CrossRefPubMed
  21. Zheng B, Wang C, Chen Q, et al. Functional Characterization of PHEX Gene Variants in Children With X-Linked Hypophosphatemic Rickets Shows No Evidence of Genotype-Phenotype Correlation. J Bone Miner Res. 2020; 35(9): 1718–1725.
    CrossRefPubMed
  22. Whyte MP, Schranck FW, Armamento-Villareal R. X-linked hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children. J Clin Endocrinol Metab. 1996; 81(11): 4075–4080.
    CrossRefPubMed
  23. Song HR, Park JW, Cho DY, et al. PHEX gene mutations and genotype-phenotype analysis of Korean patients with hypophosphatemic rickets. J Korean Med Sci. 2007; 22(6): 981–986.
    CrossRefPubMed
  24. Ruppe MD, de Beur J. Disorders of phosphate homeostasis. In: Rosen CJ. ed. Primer on the metabolic bone diseases and disorders of mineral metabolism. Wiley Blackwell, New Jersey 2013: 601–612.
  25. Boukpessi T, Altabah M, Chaussain C, et al. Endodontic Management of Patients With X Linked Hypophosphatemic Rickets: Case Series Report. Dentistry. 2017; 07(04).
    CrossRef
  26. Zivičnjak M, Schnabel D, Billing H, et al. Hypophosphatemic Rickets Study Group of Arbeitsgemeinschaft für Pädiatrische Endokrinologie and Gesellschaft für Pädiatrische Nephrologie. Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets. Pediatr Nephrol. 2011; 26(2): 223–231.
    CrossRefPubMed
  27. Murthy AS. X-linked hypophosphatemic rickets and craniosynostosis. J Craniofac Surg. 2009; 20(2): 439–442.
    CrossRefPubMed
  28. Che H, Roux C, Etcheto A, et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016; 174(3): 325–333.
    CrossRefPubMed
  29. Reid IR, Hardy DC, Murphy WA, et al. X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore). 1989; 68(6): 336–352.
    PubMed
  30. Capelli S, Donghi V, Maruca K, et al. Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets. Bone. 2015; 79: 143–149.
    CrossRefPubMed
  31. Pereira CM, de Andrade CR, Vargas PA, et al. Dental alterations associated with X-linked hypophosphatemic rickets. J Endod. 2004; 30(4): 241–245.
    CrossRefPubMed
  32. Chaussain-Miller C, Sinding C, Wolikow M, et al. Dental abnormalities in patients with familial hypophosphatemic vitamin D-resistant rickets: prevention by early treatment with 1-hydroxyvitamin D. J Pediatr. 2003; 142(3): 324–331.
    CrossRefPubMed
  33. Biosse Duplan M, Coyac BR, Bardet C, et al. Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypophosphatemia. J Dent Res. 2017; 96(4): 388–395.
    CrossRefPubMed
  34. Fishman G, Miller-Hansen D, Jacobsen C, et al. Hearing impairment in familial X-linked hypophosphatemic rickets. Eur J Pediatr. 2004; 163(10): 622–623.
    CrossRefPubMed
  35. Yuan L, Wu S, Xu H, et al. Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing. Biol Chem. 2015; 396(1): 27–33.
    CrossRefPubMed
  36. Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol. 2019; 15(7): 435–455.
    CrossRefPubMed
  37. Obara-Moszynska M, Rojek A, Kolesinska Z, et al. X-linked hypophosphataemic rickets in children: clinical phenotype, therapeutic strategies, and molecular background. Endokrynol Pol. 2021; 72(2): 108–119.
    CrossRefPubMed
  38. Imel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019; 393(10189): 2416–2427.
    CrossRefPubMed
  39. Rothenbuhler A, Esterle L, Gueorguieva I, et al. Two-year recombinant human growth hormone (rhGH) treatment is more effective in pre-pubertal compared to pubertal short children with X-linked hypophosphatemic rickets (XLHR). Growth Horm IGF Res. 2017; 36: 11–15.
    CrossRefPubMed
  40. Zhang C, Zhao Z, Sun Y, et al. Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia. Bone. 2019; 121: 212–220.
    CrossRefPubMed
  41. Wöhrle S, Henninger C, Bonny O, et al. Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013; 28(4): 899–911.
    CrossRefPubMed
  42. Fuente R, Gil-Peña H, Claramunt-Taberner D, et al. X-linked hypophosphatemia and growth. Rev Endocr Metab Disord. 2017; 18(1): 107–115.
    CrossRefPubMed
  43. Yamazaki Y, Okazaki R, Shibata M, et al. Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab. 2002; 87(11): 4957–4960.
    CrossRefPubMed
  44. Endo I, Fukumoto S, Ozono K, et al. Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone. 2008; 42(6): 1235–1239.
    CrossRefPubMed
  45. Bastepe M, Jüppner H. Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord. 2008; 9(2): 171–180.
    CrossRefPubMed
  46. ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000; 26(3): 345–348.
    CrossRefPubMed
  47. Econs MJ, McEnery PT, Lennon F, et al. Autosomal dominant hypophosphatemic rickets is linked to chromosome 12p13. J Clin Invest. 1997; 100(11): 2653–2657.
    CrossRefPubMed
  48. Takeda E, Yamamoto H, Nashiki K, et al. Inorganic phosphate homeostasis and the role of dietary phosphorus. J Cell Mol Med. 2004; 8(2): 191–200.
    CrossRefPubMed
  49. Feng JQ, Ward LM, Liu S, et al. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. 2006; 38(11): 1310–1315.
    CrossRefPubMed
  50. White KE, Carn G, Lorenz-Depiereux B, et al. Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. Kidney Int. 2001; 60(6): 2079–2086.
    CrossRefPubMed
  51. Cebeci AN, Zou M, BinEssa HA, et al. Mutation of SGK3, a Novel Regulator of Renal Phosphate Transport, Causes Autosomal Dominant Hypophosphatemic Rickets. J Clin Endocrinol Metab. 2020; 105(6).
    CrossRefPubMed
  52. White KE, Jonsson KB, Carn G, et al. The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. J Clin Endocrinol Metab. 2001; 86(2): 497–500.
    CrossRefPubMed
  53. Tournis S, Koromila T, Chatzistamatas N, et al. Hip fracture leading to the diagnosis of autosomal dominant hypophosphatemic rickets. A case report. J Musculoskelet Neuronal Interact. 2013; 13: 391–394.
    PubMed
  54. Seton M, Jüppner H. Autosomal dominant hypophosphatemic rickets in an 85 year old woman: characterization of her disease from infancy through adulthood. Bone. 2013; 52(2): 640–643.
    CrossRefPubMed
  55. Econs MJ, McEnery PT. Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder. J Clin Endocrinol Metab. 1997; 82(2): 674–681.
    CrossRefPubMed
  56. Imel EA, Hui SL, Econs MJ. FGF23 concentrations vary with disease status in autosomal dominant hypophosphatemic rickets. J Bone Miner Res. 2007; 22(4): 520–526.
    CrossRefPubMed
  57. Imel EA, Econs MJ. Approach to the hypophosphatemic patient. J Clin Endocrinol Metab. 2012; 97(3): 696–706.
    CrossRefPubMed
  58. Pettifor JM, Thandrayen K. Hypophosphatemic rickets: unraveling the role of FGF23. Calcif Tissue Int. 2012; 91(5): 297–306.
    CrossRefPubMed
  59. Gribaa M, Younes M, Bouyacoub Y, et al. An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation. J Bone Miner Metab. 2010; 28(1): 111–115.
    CrossRefPubMed
  60. Liu C, Zhao Z, Wang Ou, et al. Earlier Onset in Autosomal Dominant Hypophosphatemic Rickets of R179 than R176 Mutations in Fibroblast Growth Factor 23: Report of 20 Chinese Cases and Review of the Literature. Calcif Tissue Int. 2019; 105(5): 476–486.
    CrossRefPubMed
  61. Sun Y, Wang Ou, Xia W, et al. FGF23 analysis of a Chinese family with autosomal dominant hypophosphatemic rickets. J Bone Miner Metab. 2012; 30(1): 78–84.
    CrossRefPubMed
  62. Benet-Pagès A, Orlik P, Strom TM, et al. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Hum Mol Genet. 2005; 14(3): 385–390.
    CrossRefPubMed
  63. Larsson T, Davis SI, Garringer HJ, et al. Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are differentially processed. Endocrinology. 2005; 146(9): 3883–3891.
    CrossRefPubMed
  64. Kruse K, Woelfel D, Strom TM, et al. Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation. Horm Res. 2001; 55(6): 305–308.
    CrossRefPubMed
  65. Kinoshita Y, Fukumoto S. X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect for New Treatment. Endocr Rev. 2018; 39(3): 274–291.
    CrossRefPubMed
  66. Shimizu Y, Tada Y, Yamauchi M, et al. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone. 2009; 45(4): 814–816.
    CrossRefPubMed
  67. Imel EA, Peacock M, Gray AK, et al. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab. 2011; 96(11): 3541–3549.
    CrossRefPubMed
  68. Lorenz-Depiereux B, Bastepe M, Benet-Pagès A, et al. DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet. 2006; 38(11): 1248–1250.
    CrossRefPubMed
  69. Farrow EG, Davis SI, Ward LM, et al. Molecular analysis of DMP1 mutants causing autosomal recessive hypophosphatemic rickets. Bone. 2009; 44(2): 287–294.
    CrossRefPubMed
  70. Mäkitie O, Pereira RC, Kaitila I, et al. Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation. J Bone Miner Res. 2010; 25(10): 2165–2174.
    CrossRefPubMed
  71. Koshida R, Yamaguchi H, Yamasaki K, et al. A novel nonsense mutation in the DMP1 gene in a Japanese family with autosomal recessive hypophosphatemic rickets. J Bone Miner Metab. 2010; 28(5): 585–590.
    CrossRefPubMed
  72. Whyte MP, Amalnath SD, McAlister WH, et al. Hypophosphatemic osteosclerosis, hyperostosis, and enthesopathy associated with novel homozygous mutations of DMP1 encoding dentin matrix protein 1 and SPP1 encoding osteopontin: The first digenic SIBLING protein osteopathy? Bone. 2020; 132: 115190.
    CrossRefPubMed
  73. Lorenz-Depiereux B, Schnabel D, Tiosano D, et al. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010; 86(2): 267–272.
    CrossRefPubMed
  74. Kotwal A, Ferrer A, Kumar R, et al. Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations. J Bone Miner Res. 2020; 35(4): 662–670.
    CrossRefPubMed
  75. Rafaelsen SH, Raeder H, Fagerheim AK, et al. Exome sequencing reveals FAM20c mutations associated with fibroblast growth factor 23-related hypophosphatemia, dental anomalies, and ectopic calcification. J Bone Miner Res. 2013; 28(6): 1378–1385.
    CrossRefPubMed
  76. Simpson MA, Hsu R, Keir LS, et al. Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development. Am J Hum Genet. 2007; 81(5): 906–912.
    CrossRefPubMed
  77. Wang X, Wang S, Li C, et al. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PLoS Genet. 2012; 8(5): e1002708.
    CrossRefPubMed
  78. Harries LW, Brown JE, Gloyn AL. Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PLoS One. 2009; 4(11): e7855.
    CrossRefPubMed
  79. Mameli C, Zichichi G, Mahmood N, et al. Natural history of non-lethal Raine syndrome during childhood. Orphanet J Rare Dis. 2020; 15(1): 93.
    CrossRefPubMed
  80. Erben RG. α-Klotho's effects on mineral homeostasis are fibroblast growth factor-23 dependent. Curr Opin Nephrol Hypertens. 2018; 27(4): 229–235.
    CrossRefPubMed
  81. Rowe PS. A unified model for bone-renal mineral and energy metabolism. Curr Opin Pharmacol. 2015; 22: 64–71.
    CrossRefPubMed
  82. Smith RC, O'Bryan LM, Farrow EG, et al. Circulating αKlotho influences phosphate handling by controlling FGF23 production. J Clin Invest. 2012; 122(12): 4710–4715.
    CrossRefPubMed
  83. Tieder M, Modai D, Shaked U, et al. Hereditary hypophosphatemic rickets with hypercalciuria. N Engl J Med. 1985; 312(10): 611–617.
    CrossRefPubMed
  84. Bergwitz C, Roslin NM, Tieder M, et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet. 2006; 78(2): 179–192.
    CrossRefPubMed
  85. Lorenz-Depiereux B, Benet-Pages A, Eckstein G, et al. Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet. 2006; 78(2): 193–201.
    CrossRefPubMed
  86. Dhir G, Li D, Hakonarson H, et al. Late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to mutation of SLC34A3/NPT2c. Bone. 2017; 97: 15–19.
    CrossRefPubMed
  87. Page K, Bergwitz C, Jaureguiberry G, et al. A patient with hypophosphatemia, a femoral fracture, and recurrent kidney stones: report of a novel mutation in SLC34A3. Endocr Pract. 2008; 14(7): 869–874.
    CrossRefPubMed
  88. Braithwaite V, Pettifor JM, Prentice A. Novel SLC34A3 mutation causing hereditary hypophosphataemic rickets with hypercalciuria in a Gambian family. Bone. 2013; 53(1): 216–220.
    CrossRefPubMed
  89. Hasani-Ranjbar S, Amoli MM, Ebrahim-Habibi A, et al. SLC34A3 intronic deletion in a new kindred with hereditary hypophosphatemic rickets with hypercalciuria. J Clin Res Pediatr Endocrinol. 2012; 4(2): 89–93.
    CrossRefPubMed
  90. Wagner CA, Rubio-Aliaga I, Hernando N. Renal phosphate handling and inherited disorders of phosphate reabsorption: an update. Pediatr Nephrol. 2019; 34(4): 549–559.
    CrossRefPubMed
  91. Dasgupta D, Wee MJ, Reyes M, et al. Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis. J Am Soc Nephrol. 2014; 25(10): 2366–2375.
    CrossRefPubMed
  92. Ichikawa S, Tuchman S, Padgett LR, et al. Intronic deletions in the SLC34A3 gene: a cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. Bone. 2014; 59: 53–56.
    CrossRefPubMed
  93. Hasani-Ranjbar S, Ejtahed HS, Amoli MM, et al. Intronic Deletion in an Iranian Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria. J Clin Res Pediatr Endocrinol. 2018; 10(4): 343–349.
    CrossRefPubMed
  94. Gordon RJ, Li D, Doyle D, et al. Digenic Heterozygous Mutations in SLC34A3 and SLC34A1 Cause Dominant Hypophosphatemic Rickets with Hypercalciuria. J Clin Endocrinol Metab. 2020; 105(7).
    CrossRefPubMed
  95. Lloyd SE, Pearce SH, Fisher SE, et al. A common molecular basis for three inherited kidney stone diseases. Nature. 1996; 379(6564): 445–449.
    CrossRefPubMed
  96. Fisher SE, van Bakel I, Lloyd SE, et al. Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis). Genomics. 1995; 29(3): 598–606.
    CrossRefPubMed
  97. Günther W, Lüchow A, Cluzeaud F, et al. ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells. Proc Natl Acad Sci U S A. 1998; 95(14): 8075–8080.
    CrossRefPubMed
  98. Scheinman SJ. X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations. Kidney Int. 1998; 53(1): 3–17.
    CrossRefPubMed
  99. Gambaro G, Vezzoli G, Casari G, et al. Genetics of hypercalciuria and calcium nephrolithiasis: from the rare monogenic to the common polygenic forms. Am J Kidney Dis. 2004; 44(6): 963–986.
    CrossRefPubMed
  100. Bolino A, Devoto M, Enia G, et al. Genetic mapping in the Xp11.2 region of a new form of X-linked hypophosphatemic rickets. Eur J Hum Genet. 1993; 1(4): 269–279.
    CrossRefPubMed
  101. Oudet C, Martin-Coignard D, Pannetier S, et al. A second family with XLRH displays the mutation S244L in the CLCN5 gene. Hum Genet. 1997; 99(6): 781–784.
    CrossRefPubMed
  102. Dixon PH, Christie PT, Wooding C, et al. Mutational analysis of PHEX gene in X-linked hypophosphatemia. J Clin Endocrinol Metab. 1998; 83(10): 3615–3623.
    CrossRefPubMed
  103. Tyynismaa H, Kaitila I, Näntö-Salonen K, et al. Identification of fifteen novel PHEX gene mutations in Finnish patients with hypophosphatemic rickets. Hum Mutat. 2000; 15(4): 383–384, doi: 10.1002/(SICI)1098-1004(200004)15:4<383::AID-HUMU18>3.0.CO;2-#.
    PubMed
  104. Goji K, Ozaki K, Sadewa AH, et al. Somatic and germline mosaicism for a mutation of the PHEX gene can lead to genetic transmission of X-linked hypophosphatemic rickets that mimics an autosomal dominant trait. J Clin Endocrinol Metab. 2006; 91(2): 365–370.
    CrossRefPubMed
  105. Xia W, Meng X, Jiang Y, et al. Three novel mutations of the PHEX gene in three Chinese families with X-linked dominant hypophosphatemic rickets. Calcif Tissue Int. 2007; 81(6): 415–420.
    CrossRefPubMed
  106. Ichikawa S, Traxler EA, Estwick SA, et al. Mutational survey of the PHEX gene in patients with X-linked hypophosphatemic rickets. Bone. 2008; 43(4): 663–666.
    CrossRefPubMed
  107. Saito T, Nishii Y, Yasuda T, et al. Familial hypophosphatemic rickets caused by a large deletion in PHEX gene. Eur J Endocrinol. 2009; 161(4): 647–651.
    CrossRefPubMed
  108. Gaucher C, Walrant-Debray O, Nguyen TM, et al. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets. Hum Genet. 2009; 125(4): 401–411.
    CrossRefPubMed
  109. Beck-Nielsen SS, Brusgaard K, Rasmussen LM, et al. Phenotype presentation of hypophosphatemic rickets in adults. Calcif Tissue Int. 2010; 87(2): 108–119.
    CrossRefPubMed
  110. Morey M, Castro-Feijóo L, Barreiro J, et al. Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type. BMC Med Genet. 2011; 12: 116.
    CrossRefPubMed
  111. Beck-Nielsen SS, Brixen K, Gram J, et al. Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J Hum Genet. 2012; 57(7): 453–458.
    CrossRefPubMed
  112. Kinoshita Y, Saito T, Shimizu Y, et al. Mutational analysis of patients with FGF23-related hypophosphatemic rickets. Eur J Endocrinol. 2012; 167(2): 165–172.
    CrossRefPubMed
  113. Durmaz E, Zou M, Al-Rijjal RA, et al. Novel and de novo PHEX mutations in patients with hypophosphatemic rickets. Bone. 2013; 52(1): 286–291.
    CrossRefPubMed
  114. Dayal D, Sharda S, Attri SV, et al. Hypophosphatemic rickets caused by a novel PHEX gene mutation in an Indian girl. J Pediatr Endocrinol Metab. 2014; 27(7-8): 787–789.
    CrossRefPubMed
  115. Pekkarinen T, Lorenz-Depiereux B, Lohman M, et al. Unusually severe hypophosphatemic rickets caused by a novel and complex re-arrangement of the PHEX gene. Am J Med Genet A. 2014; 164A(11): 2931–2937.
    CrossRefPubMed
  116. Radlović V, Smoljanić Z, Radlović N, et al. X-linked hypophosphatemic rickets: case report. Srp Arh Celok Lek. 2014; 142(1-2): 75–78.
    CrossRefPubMed
  117. Mumm S, Huskey M, Cajic A, et al. PHEX 3'-UTR c.*231A>G near the polyadenylation signal is a relatively common, mild, American mutation that masquerades as sporadic or X-linked recessive hypophosphatemic rickets. J Bone Miner Res. 2015; 30(1): 137–143.
    CrossRefPubMed
  118. Ma SL, Vega-Warner V, Gillies C, et al. Whole Exome Sequencing Reveals Novel PHEX Splice Site Mutations in Patients with Hypophosphatemic Rickets. PLoS One. 2015; 10(6): e0130729.
    CrossRefPubMed
  119. Rafaelsen S, Johansson S, Ræder H, et al. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol. 2016; 174(2): 125–136.
    CrossRefPubMed
  120. Weng C, Chen J, Sun Li, et al. A de novo mosaic mutation of PHEX in a boy with hypophosphatemic rickets. J Hum Genet. 2016; 61(3): 223–227.
    CrossRefPubMed
  121. Gu J, Wang C, Zhang H, et al. Targeted resequencing of phosphorus metabolism‑related genes in 86 patients with hypophosphatemic rickets/osteomalacia. Int J Mol Med. 2018; 42(3): 1603–1614.
    CrossRefPubMed
  122. Rothenbuhler A, Fadel N, Debza Y, et al. High Incidence of Cranial Synostosis and Chiari I Malformation in Children With X-Linked Hypophosphatemic Rickets (XLHR). J Bone Miner Res. 2019; 34(3): 490–496.
    CrossRefPubMed
  123. Guerboub AA, Moussaoui S, Issouani J, et al. X-linked vitamin D-resistant rickets: 12 years of follow-up. Pan Afr Med J. 2018; 30: 9.
    CrossRefPubMed
  124. Acar S, BinEssa HA, Demir K, et al. Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3. PLoS One. 2018; 13(3): e0193388.
    CrossRefPubMed
  125. Goljanek-Whysall K, Tridimas A, McCormick R, et al. Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia. Bone. 2018; 106: 30–34.
    CrossRefPubMed
  126. Yang M, Kim J, Yang A, et al. A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets. Ann Pediatr Endocrinol Metab. 2018; 23(4): 229–234.
    CrossRefPubMed
  127. Jin P, Wang LH, Mo ZH. Identification a novel insertion PHEX mutation in a sporadic patient with hypophosphatemic rickets. J Endocrinol Invest. 2019; 42(3): 357–359.
    CrossRefPubMed
  128. Sako S, Niida Yo, Shima KR, et al. A novel mutation associated with vitamin D-resistant rickets. Hum Genome Var. 2019; 6: 9.
    CrossRefPubMed
  129. Lee KS, Lee BoL. The first Korean case report with scaphocephaly as the initial sign of X-linked hypophosphatemic rickets. Childs Nerv Syst. 2019; 35(6): 1045–1049.
    CrossRefPubMed
  130. Li W, Tan L, Li X, et al. Identification of a p.Trp403* nonsense variant in PHEX causing X-linked hypophosphatemia by inhibiting p38 MAPK signaling. Hum Mutat. 2019; 40(7): 879–885.
    CrossRefPubMed
  131. Şıklar Z, Turan S, Bereket A, et al. Nationwide Turkish Cohort Study of Hypophosphatemic Rickets. J Clin Res Pediatr Endocrinol. 2020; 12(2): 150–159.
    CrossRefPubMed
  132. Razali NN, Tzer HT, King HL, et al. Predicting the Impact of PHEX, FGF23 and DMP1 Gene Variants Found in Malaysian Malay Patients with Hypophosphataemic Rickets Through In Silico Analysis of Protein Function and mRNA Secondary Structure. J Biochem Microbiol Biotechnol. 2019; 7: 14–23.
  133. Lin Y, Xu J, Li X, et al. Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia. J Endocrinol Invest. 2020; 43(11): 1577–1590.
    CrossRefPubMed
  134. Zhao Y, Yang F, Wang L, et al. Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation. J Pediatr Endocrinol Metab. 2020; 33(2): 305–311.
    CrossRefPubMed
  135. Mualla H, Bae SuAh, Yaqub A. Autosomal Dominant Hypophosphatemic Rickets Presenting in a Phenotypically Normal Adult Female. Case Rep Endocrinol. 2019; 2019: 8917519.
    CrossRefPubMed
  136. Turan S, Aydin C, Bereket A, et al. Identification of a novel dentin matrix protein-1 (DMP-1) mutation and dental anomalies in a kindred with autosomal recessive hypophosphatemia. Bone. 2010; 46(2): 402–409.
    CrossRefPubMed
  137. Levy-Litan V, Hershkovitz E, Avizov L, et al. Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet. 2010; 86(2): 273–278.
    CrossRefPubMed
  138. Saito T, Shimizu Y, Hori M, et al. A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene. Bone. 2011; 49(4): 913–916.
    CrossRefPubMed
  139. Chi Y, Zhao Z, He X, et al. A compound heterozygous mutation in SLC34A3 causes hereditary hypophosphatemic rickets with hypercalciuria in a Chinese patient. Bone. 2014; 59: 114–121.
    CrossRefPubMed
  140. Tang A, Hinz L, Khan A, et al. Phosphate matters when investigating hypercalcemia: a mutation in SLC34A3 causing HHRH. Endocrinol Diabetes Metab Case Rep. 2019; 2019(1): 1–6.
    CrossRefPubMed
  141. Chen A, Ro H, Mundra VR, et al. Description of 5 Novel NPT2c Mutations Causing Hereditary Hypophosphatemic Rickets With Hypercalciuria. Kidney Int Rep. 2019; 4(8): 1179–1186.
    CrossRefPubMed

About cookies

Necessary cookies

Allways active

These cookies are necessary for the proper display and operation of the website. Blocking them may cause the website to malfunction.

Analytical cookies

As part of our website, we use analytical tools, such as Google Analytics, that allow us to verify website traffic. These tools may require the use of cookies.

Community cookies

These are cookies associated with the social networks we use. Accepting them will allow us to associate your visit to the site with our social media profiles.

Marketing cookies

These are cookies responsible for carrying out advertising and marketing activities - consenting to their use will allow us to target you with advertisements based on your previous activities within our website.

Copyright © 2023-2024 Via Medica Regulations Cookie policy Privacy Statement Legal Note