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Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria.

Publication ,  Journal Article
Ichikawa, S; Sorenson, AH; Imel, EA; Friedman, NE; Gertner, JM; Econs, MJ
Published in: J Clin Endocrinol Metab
October 2006

CONTEXT: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia and rickets/osteomalacia with increased serum 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] resulting in hypercalciuria. OBJECTIVE: Our objective was to determine whether mutations in the SLC34A3 gene, which encodes sodium-phosphate cotransporter type IIc, are responsible for the occurrence of HHRH. DESIGN AND SETTING: Mutation analysis of exons and adjacent introns in the SLC34A3 gene was conducted at an academic research laboratory and medical center. PATIENTS OR OTHER PARTICIPANTS: Members of two unrelated families with HHRH participated in the study. RESULTS: Two affected siblings in one family were homozygous for a 101-bp deletion in intron 9. Haplotype analysis of the SLC34A3 locus in the family showed that the two deletions are on different haplotypes. An unrelated individual with HHRH was a compound heterozygote for an 85-bp deletion in intron 10 and a G-to-A substitution at the last nucleotide in exon 7. The intron 9 deletion (and likely the other two mutations) identified in this study causes aberrant RNA splicing. Sequence analysis of the deleted regions revealed the presence of direct repeats of homologous sequences. CONCLUSION: HHRH is caused by biallelic mutations in the SLC34A3 gene. Haplotype analysis suggests that the two intron 9 deletions arose independently. The identification of three independent deletions in introns 9 and 10 suggests that the SLC34A3 gene may be susceptible to unequal crossing over because of sequence misalignment during meiosis.

Duke Scholars

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

October 2006

Volume

91

Issue

10

Start / End Page

4022 / 4027

Location

United States

Related Subject Headings

  • Sodium-Phosphate Cotransporter Proteins, Type IIc
  • Mutation
  • Molecular Sequence Data
  • Kidney Calculi
  • Introns
  • Infant
  • Hypophosphatemia, Familial
  • Humans
  • Gene Deletion
  • Endocrinology & Metabolism
 

Citation

APA
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MLA
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Ichikawa, S., Sorenson, A. H., Imel, E. A., Friedman, N. E., Gertner, J. M., & Econs, M. J. (2006). Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab, 91(10), 4022–4027. https://doi.org/10.1210/jc.2005-2840
Ichikawa, Shoji, Andrea H. Sorenson, Erik A. Imel, Nancy E. Friedman, Joseph M. Gertner, and Michael J. Econs. “Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria.J Clin Endocrinol Metab 91, no. 10 (October 2006): 4022–27. https://doi.org/10.1210/jc.2005-2840.
Ichikawa S, Sorenson AH, Imel EA, Friedman NE, Gertner JM, Econs MJ. Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab. 2006 Oct;91(10):4022–7.
Ichikawa, Shoji, et al. “Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria.J Clin Endocrinol Metab, vol. 91, no. 10, Oct. 2006, pp. 4022–27. Pubmed, doi:10.1210/jc.2005-2840.
Ichikawa S, Sorenson AH, Imel EA, Friedman NE, Gertner JM, Econs MJ. Intronic deletions in the SLC34A3 gene cause hereditary hypophosphatemic rickets with hypercalciuria. J Clin Endocrinol Metab. 2006 Oct;91(10):4022–4027.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

October 2006

Volume

91

Issue

10

Start / End Page

4022 / 4027

Location

United States

Related Subject Headings

  • Sodium-Phosphate Cotransporter Proteins, Type IIc
  • Mutation
  • Molecular Sequence Data
  • Kidney Calculi
  • Introns
  • Infant
  • Hypophosphatemia, Familial
  • Humans
  • Gene Deletion
  • Endocrinology & Metabolism