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A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene.
Bone. 2011 Oct; 49(4):913-6.BONE

Abstract

X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR1 or ARHR2) are hereditary fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets showing similar clinical features. We here show a patient with hypophosphatemic rickets and widespread ossification of posterior longitudinal ligament (OPLL). The proband is a 62-year-old female. Her parents are first cousins and showed no signs of rickets or osteomalacia. She showed hypophosphatemic rickets with elevated FGF23 level and had been clinically considered to be suffering from XLH. However, direct sequencing of all coding exons and exon-intron junctions of phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX), FGF23 and dentin matrix protein 1 (DMP1) genes, responsible genes for XLH, ADHR and ARHR1, respectively, showed no mutation. A novel homozygous splice donor site mutation was found at the exon-intron junction of exon 21 of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene responsible for ARHR2 (IVS21+1_3(GTA>CACC)). Subsequent analysis of mRNA revealed that this mutation caused skipping of exon 21 which created a premature stop codon in exon 22. These results indicate that genetic analysis is mandatory for the correct diagnosis of hereditary FGF23-related hypophosphatemic rickets. Because Enpp1 knockout mouse is a model of OPLL, this case also suggests that OPLL is associated with ARHR2.

Authors+Show Affiliations

Division of Pediatrics, University of Tokyo Hospital, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21745613

Citation

Saito, Tasuku, et al. "A Patient With Hypophosphatemic Rickets and Ossification of Posterior Longitudinal Ligament Caused By a Novel Homozygous Mutation in ENPP1 Gene." Bone, vol. 49, no. 4, 2011, pp. 913-6.
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):913-6.
Saito, T., Shimizu, Y., Hori, M., Taguchi, M., Igarashi, T., Fukumoto, S., & Fujitab, T. (2011). A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene. Bone, 49(4), 913-6. https://doi.org/10.1016/j.bone.2011.06.029
Saito T, 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):913-6. PubMed PMID: 21745613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene. AU - Saito,Tasuku, AU - Shimizu,Yuichiro, AU - Hori,Michiko, AU - Taguchi,Manabu, AU - Igarashi,Takashi, AU - Fukumoto,Seiji, AU - Fujitab,Toshiro, Y1 - 2011/07/02/ PY - 2011/04/30/received PY - 2011/06/13/revised PY - 2011/06/23/accepted PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2011/12/22/medline SP - 913 EP - 6 JF - Bone JO - Bone VL - 49 IS - 4 N2 - X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR1 or ARHR2) are hereditary fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets showing similar clinical features. We here show a patient with hypophosphatemic rickets and widespread ossification of posterior longitudinal ligament (OPLL). The proband is a 62-year-old female. Her parents are first cousins and showed no signs of rickets or osteomalacia. She showed hypophosphatemic rickets with elevated FGF23 level and had been clinically considered to be suffering from XLH. However, direct sequencing of all coding exons and exon-intron junctions of phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX), FGF23 and dentin matrix protein 1 (DMP1) genes, responsible genes for XLH, ADHR and ARHR1, respectively, showed no mutation. A novel homozygous splice donor site mutation was found at the exon-intron junction of exon 21 of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene responsible for ARHR2 (IVS21+1_3(GTA>CACC)). Subsequent analysis of mRNA revealed that this mutation caused skipping of exon 21 which created a premature stop codon in exon 22. These results indicate that genetic analysis is mandatory for the correct diagnosis of hereditary FGF23-related hypophosphatemic rickets. Because Enpp1 knockout mouse is a model of OPLL, this case also suggests that OPLL is associated with ARHR2. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/21745613/A_patient_with_hypophosphatemic_rickets_and_ossification_of_posterior_longitudinal_ligament_caused_by_a_novel_homozygous_mutation_in_ENPP1_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(11)01070-2 DB - PRIME DP - Unbound Medicine ER -