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  • Test code: 72039
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Hypophosphatemia Panel

Test description

The genetic forms of hypophosphatemia are heterogeneous conditions which are characterized by abnormal phosphate levels leading to abnormal growth of bones and teeth.

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Primary panel (17 genes)

ALPL CLCN5 CTNS CYP27B1 CYP2R1 DMP1 ENPP1 FAH FAM20C FGF23 FGFR1 GNAS OCRL PHEX SLC34A1 SLC34A3 VDR

  • Hypophosphatasia
  • Dent disease
  • Cystinosis
  • Vitamin D-dependent rickets, type I
  • Vitamin D-hydroxylation deficient rickets type IB
  • Hypophosphatemic rickets 1
  • Hypophosphatemic rickets 2 (ARHR2)
  • Tyrosinemia type 1
  • Raine syndrome (RNS)
  • Hypophosphatemic rickets (ADHR), Hyperphosphatemic familial tumoral calcinosis (HFTC)
  • Kallmann syndrome 2, Hartsfield syndrome, osteoglophonic dysplasia
  • Progressive osseous heteroplasia, pseudohypoparathyroidism Ia, pseudopseudohypoparathyroidism, and McCune-Albright syndrome
  • Lowe syndrome
  • X-linked hypophosphatemia (XLH)
  • Infantile hypercalcemia, Hypophosphatemic nephrolithiasis/osteoporosis, Fanconi renotubular syndrome
  • Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
  • Vitamin D-dependent rickets type 2A (VDDR2A)

To view the complete clinical description of this panel, click here.

The most common form of hypophosphatemia is the X-linked dominant form (XLH) with other forms showing autosomal recessive and/or autosomal dominant inheritance.

  1. Chesher, D, et al. Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J. Inherit. Metab. Dis. 2018; 41(5):865-876. PMID: 29460029
  2. Fuente, R, et al. X-linked hypophosphatemia and growth. Rev Endocr Metab Disord. 2017; 18(1):107-115. PMID: 28130634
  3. Beck-Nielsen, SS, et al. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur. J. Endocrinol. 2009; 160(3):491-7. PMID: 19095780
  4. Acar, S, et al. Clinical and genetic characteristics of 15 families with hereditary hypophosphatemia: Novel Mutations in PHEX and SLC34A3. PLoS ONE. 2018; 13(3):e0193388. PMID: 29505567
  5. Beck-Nielsen, SS, et al. Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J. Hum. Genet. 2012; 57(7):453-8. PMID: 22695891
  6. Ruppe, MD. X-Linked Hypophosphatemia. 2012 Feb 09. In: Adam, MP, et al, editors. GeneReviews® (Internet). University of Washington, Seattle. PMID: 22319799
  7. Bacchetta, J, et al. Physiology of FGF23 and overview of genetic diseases associated with renal phosphate wasting. Metab. Clin. Exp. 2019; :None. PMID: 30664852
  8. Faiyaz-Ul-Haque, M, et al. Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation. J. Pediatr. Endocrinol. Metab. 2018; 31(8):861-868. PMID: 29949513
  9. Carpenter, TO. The expanding family of hypophosphatemic syndromes. J. Bone Miner. Metab. 2012; 30(1):1-9. PMID: 22167381
  10. Devuyst, O, Thakker, RV. Dent's disease. Orphanet J Rare Dis. 2010; 5:28. PMID: 20946626
  11. Whyte, MP, et al. Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients. Bone. 2015; 75:229-39. PMID: 25731960
  12. Oyachi, M, et al. A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: clinical course and review of the literature. Clin Pediatr Endocrinol. 2018; 27(3):179-186. PMID: 30083035
  13. Capelli S, et al. Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets. Bone. 2015; 79:143-9. PMID: 26051471
  14. Mornet, E, et al. A molecular-based estimation of the prevalence of hypophosphatasia in the European population. Ann. Hum. Genet. 2011; 75(3):439-45. PMID: 21488855
  15. Mornet, E. Genetics of hypophosphatasia. Arch Pediatr. 2017; 24(5S2):5S51-5S56. PMID: 29405932
  16. Claverie-Martín, F, et al. Dent's disease: clinical features and molecular basis. Pediatr. Nephrol. 2011; 26(5):693-704. PMID: 20936522
  17. Carpenter, TO, et al. A clinician's guide to X-linked hypophosphatemia. J. Bone Miner. Res. 2011; 26(7):1381-8. PMID: 21538511

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALPL NM_000478.5
CLCN5 NM_000084.4
CTNS NM_004937.2
CYP27B1 NM_000785.3
CYP2R1 NM_024514.4
DMP1 NM_004407.3
ENPP1 NM_006208.2
FAH* NM_000137.2
FAM20C NM_020223.3
FGF23 NM_020638.2
FGFR1 NM_023110.2
GNAS NM_000516.5
OCRL NM_000276.3
PHEX* NM_000444.5
SLC34A1 NM_003052.4
SLC34A3 NM_080877.2
VDR NM_001017535.1

FAH: Deletion/duplication analysis is not offered for exon 14.
PHEX: Analysis includes the NM_000444.5:c.*231A>G variant.