Intronic deletions in the SLC34A3 gene

A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

Shoji Ichikawa, Shamir Tuchman, Leah R. Padgett, Amie K. Gray, H. Jorge Baluarte, Michael Econs

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6-1/2-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24-hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH), and elevated 1,25(OH)2D. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440-1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH.

Original languageEnglish (US)
Pages (from-to)53-56
Number of pages4
JournalBone
Volume59
DOIs
StatePublished - 2014

Fingerprint

Introns
Mutation
Base Pairing
Rickets
Genes
Phosphorus
Sodium-Phosphate Cotransporter Proteins
Serum
Urine
Calcium
RNA Splicing
Hypophosphatemia
Symporters
Hypercalciuria
Nephrolithiasis
Osteomalacia
Nonsense Codon
Heterozygote
Parathyroid Hormone
Exons

Keywords

  • Deletion
  • HHRH
  • Hypercalciuria
  • Hypophosphatemia
  • Intron
  • Nephrolithiasis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Intronic deletions in the SLC34A3 gene : A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. / Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael.

In: Bone, Vol. 59, 2014, p. 53-56.

Research output: Contribution to journalArticle

Ichikawa, Shoji ; Tuchman, Shamir ; Padgett, Leah R. ; Gray, Amie K. ; Baluarte, H. Jorge ; Econs, Michael. / Intronic deletions in the SLC34A3 gene : A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria. In: Bone. 2014 ; Vol. 59. pp. 53-56.
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