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A Novel GALNT3 Mutation in a Pseudoautosomal Dominant Form of Tumoral Calcinosis: Evidence That the Disorder Is Autosomal Recessive

Departments of Medicine (S.I., M.J.E.) and Medical and Molecular Genetics (M.J.E.), Indiana University School of Medicine, Indianapolis, Indiana 46202; and Department of Medicine (K.W.L.), Duke University Medical Center and Geriatric Research Education and Clinical Center, Veterans Affairs Medical Center, Durham, North Carolina 27710

Address all correspondence and requests for reprints to: Michael J. Econs, M.D., Department of Medicine, Indiana University School of Medicine, 541 North Clinical Drive, Clinical Building 459, Indianapolis, Indiana 46202-5121. E-mail: mecons{at}iupui.edu.

Abstract

Familial tumoral calcinosis is a rare metabolic disorder, characterized by ectopic calcification and hyperphosphatemia. Recently biallelic mutations in the GalNAc transferase 3 (GALNT3) gene were identified in two families with tumoral calcinosis. In the present study, we performed mutation analysis of the GALNT3 gene in a multigenerational family, which was originally described to have an autosomal dominant form of tumoral calcinosis. We identified a novel splice site mutation in intron 1 (IVS1–2at), likely leading to skipping of exon 2. The proband was a compound heterozygote for the splice site mutation and the previously reported nonsense mutation (484CT; R162X). His affected maternal great uncle was homozygous for the splice site mutation. Biallelic mutations found in two generations demonstrated that the family had pseudoautosomal dominant inheritance, confirming that tumoral calcinosis is in fact an autosomal recessive trait. However, genetic and biochemical findings suggest that carriers of a single mutation may also manifest subtle biochemical abnormalities. Furthermore, coexpression of GALNT3 and fibroblast growth factor 23 (FGF23), a key regulator of phosphate homeostasis, in certain tissues suggests that O-glycosylation of FGF23 by GALNT3 may be necessary for proper function of FGF23.

FAMILIAL TUMORAL calinosis (OMIM no. 211900) is a rare metabolic disorder, characterized by the presence of ectopic periarticular calcifications and hyperphosphatemia. The occurrence of the disease is often associated with dental abnormalities and inappropriately normal or elevated levels of serum 1,25-dihydroxyvitamin D [1,25-(OH)₂D; calcitriol]. Although most families with tumoral calcinosis show autosomal recessive inheritance (1, 2, 3, 4), an autosomal dominant form with nine affected individuals in four successive generations has also been described (5). Recently, biallelic mutations in the UDP-N-acetyl--D-galactosamine/polypeptide N-acetylgalactosaminyl transferase 3 (GalNAc transferase 3 or GALNT3) gene were established as the molecular cause of recessive forms of tumoral calcinosis in two families (6). In the current study, we performed mutation analysis of the GALNT3 gene in the previously reported multigenerational kindred with a presumed autosomal dominant form of tumoral calcinosis (5) to determine whether this gene is also responsible for the appearance of the disease in this kindred.

Subjects and Methods

Study subjects

The current family is African-American and was originally described by McPhaul and Engel (1) and Lyles et al. (5). The family pedigree is shown in Fig. 1A. The proband (IV-6), his maternal grandfather (II-3), and his great uncle (II-5) have classical manifestations of tumoral calcinosis, including tumorous calcific masses, hyperphosphatemia [range 5.50–7.30 mg/dl (1.78–2.36 mmol/liter)], and elevated serum 1,25-(OH)₂D level [59.8–88.6 pg/ml (155.5–230.4 pmol/liter)] (5). A unique dental lesion (short bulbous roots, pulp stones, and radicular dentin deposited in swirls) associated with the disease was present in the proband and his great uncle (5). The proband’s mother (III-8) and great grandfather (I-1) were described to have elevated 1,25-(OH)₂D levels, and the mother was also hyperphosphatemic (5). Four other family members in this kindred (not shown in Fig. 1A) were also described to have elevated serum 1,25-(OH)₂D concentration, dental abnormality, and/or calcific tumors (5). Therefore, the transmission of tumoral calcinosis in this family was previously described to be autosomal dominant with variable clinical expression (5). Written informed consent was obtained from all subjects before their participation in the study. The study was approved by the Institutional Review Board of both Duke University and Indiana University-Purdue University Indianapolis.

View larger version (31K): [in this window] [in a new window]   FIG. 1. Family pedigree and mutation analysis. A, A pedigree of a kindred showing apparent autosomal dominant inheritance of tumoral calcinosis. Circles denote female subjects; squares denote male subjects. Filled symbols denote affected individuals. Symbols with hashed lines indicate individuals who were described to have hyperphosphatemia and/or elevated 1,25-(OH)2D level but no calcified deposits. An arrow indicates the proband. Symbols with an oblique line indicate deceased family members. The generations are labeled as I-IV, and the individuals within each generation are designated with numbers as in the original publication (5 ). B, Sequence analysis of the GALNT3 gene. Electropherograms of PCR amplicons encompassing exons 1 and 2 in the GALNT3 gene are shown. C-to-T inversion in exon 1 (484 CT; R162X) and A-to-T transversion in intron 1 (IVS1–2at) are indicated by an arrow. C, PCR-RFLP analysis of two GALNT3 mutations. The R162X mutation creates a novel DdeI restriction site and thus produces two additional fragments (139 and 31 bp) that are absent in the digest of the normal allele (170 and 84 bp). The 31-bp fragment is not shown. The IVS1–2at mutation disrupts an XbaI restriction site. Therefore, after incubation with XbaI, the disease allele is intact (469 bp), whereas the normal allele generates two fragments (279 and 190 bp).

Genomic DNA was extracted from blood collected from the proband (IV-6) and his parents (III-7 and III-8), using standard procedures. All 10 GALNT3 coding exons, as well as conserved splice sites, were amplified in nine fragments by standard PCR methods. Primer sequences are available on request. Individuals in the first and second generations are deceased. However, a surgical specimen from individual II-5 was available. DNA for this individual was extracted from paraffin-embedded synovial tissue from a total hip replacement, using QIAamp tissue mini kit (QIAGEN Inc., Valencia, CA). Due to a limited amount of DNA obtained from the tissue, not all exons in this individual were analyzed.

PCR products were electrophoresed in a 2% agarose gel and purified, using DNA gel extraction kit (QIAGEN). Approximately 100 ng of each PCR amplicon was directly sequenced from forward primers, using Big-Dye terminator cycle sequencing kit and the ABI PRISM 3100 genetic analyzer (PE Applied Biosystems, Foster City, CA). Mutations were identified by BLAST2 comparisons with the GALNT3 genomic sequence obtained through Human May 2004 (hg17) assembly of the University of California Santa Cruz Genome Browser (www.genome.ucsc.edu).

PCR-restriction fragment length polymorphism (RFLP) analysis

Genomic DNA fragments containing a nonsense mutation in exon 1 and a splice site mutation in intron 1 were amplified by standard PCR methods. PCR products were then subjected to 5 U of DdeI (New England Biolabs, Beverly, MA) and 30 U of XbaI (New England Biolabs), respectively. After incubation at 37 C for 16 h, digested PCR products were electrophoresed in a 2% agarose gel and visualized under the UV light.

RT-PCR analysis

First-strand cDNAs were synthesized from 1 µg each of total RNAs, using BD Advantage RT-for-PCR kit (BD Biosciences Clontech, Palo Alto, CA). Total RNAs used in the cDNA synthesis were from 11 tissues and one cell line: small intestine; heart; spinal cord; prostate; spleen; testis; stomach; thyroid; trachea on Human Total RNA Master Panel II (BD Biosciences Clontech); bone (Stratagene, La Jolla, CA); liver (BD Biosciences Clontech); and osteogenic sarcoma cell line (Ambion, Inc., Austin, TX). The synthesized cDNA was then used for PCR amplification of GALNT3, fibroblast growth factor (FGF23), and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) transcripts. The RT-PCR products were resolved on a 2% agarose gels and visualized under the UV light.

Results

Analysis of the GALNT3 genomic sequence demonstrated that the proband (IV-6) is a compound heterozygote for the previously reported nonsense mutation (484CT; R162X) in exon 1 (6) and a novel at transversion in intron 1 (IVS1–2at), which disrupts a consensus splice acceptor site sequence (Fig. 1B). His mother (III-8) carries the same splice site mutation, whereas his father (III-7) carries the nonsense mutation. No other mutations were found in either parent. The maternal great-uncle (II-5) was homozygous for the splice site mutation (Fig. 1B).

To confirm cosegregation of the mutations with the disease, we performed PCR-RFLP analysis for this family (Fig. 1C). The nonsense mutation in exon 1 creates a new DdeI restriction site (6), producing two additional fragments (139 and 31 bp) in the mutant allele after the digestion. The normal allele generates two fragments of 170 and 84 bp. The splice site mutation in intron 1 disrupts an XbaI recognition site in PCR amplicon encompassing exon 2. Therefore, after incubation with XbaI, the mutant allele is intact (469 bp), whereas the normal allele generates 279- and 190-bp fragments. These two mutations were not found in at least 70 healthy unrelated African-Americans.

Gene expression of GALNT3 and FGF23 genes was assessed by RT-PCR analysis of 11 different tissues and one cell line. GALNT3 was rather ubiquitously expressed. GALNT3 and FGF23 were coexpressed in small intestine, heart, prostate, testis, thyroid, trachea, bone, and liver (Fig. 2). Expression of a housekeeping gene, G3PDH, was comparable in all samples analyzed.

View larger version (43K): [in this window] [in a new window]   FIG. 2. Coexpression of GALNT3 and FGF23 genes. Gene expression of GALNT3 and FGF23 in 11 different tissues and one cell line were assessed by RT-PCR analysis. PCR amplification of the G3PDH gene indicates successful reverse transcription of total RNAs.

Recently mutations in the GALNT3 gene were identified in two families with an autosomal recessive form of tumoral calcinosis (6). The current kindred has affected individuals in four generations and was previously described to have a dominant form of the disease because the clinical data were most consistent with a dominant disorder with variable expressivity (5). Sequence analysis of the GALNT3 gene in this kindred demonstrated that two individuals with classical phenotypes (II-5 and IV-6) carry biallelic mutations (R162X and/or IVS1–2at). The R162X mutation results in premature termination of protein translation. The splice site mutation is expected to cause skipping of exon 2, resulting in deletion of a critical domain of GALNT3 protein. Although DNA from the proband’s grandfather (II-3) was unavailable, he was also likely homozygous for the splice site mutation. These findings are consistent with autosomal recessive inheritance. However, the proband’s mother (III-8) and great grandfather (I-1) as well as other members in this family are known to have hyperphosphatemia and/or elevated 1,25-(OH)₂D levels (5). Review of biochemical profiles in members of the other previously described families also indicates that suspected heterozygotes often had increased serum phosphate and/or elevated 1,25-(OH)₂D concentrations (3, 4). These observations suggest that, even though manifestation of the classical clinical phenotype of tumoral calcinosis requires two mutations, one mutation may be sufficient to cause subtle biochemical abnormalities.

The biochemical hallmark of tumoral calcinosis is hyperphosphatemia (increased retention of renal phosphate in kidney), which is associated with inappropriately normal or elevated levels of 1,25-(OH)₂D. In contrast, mutations in genes encoding key regulators of serum phosphate, PHEX, and FGF23 cause X-linked hypophosphatemia and autosomal dominant hypophosphatemic rickets, respectively. These diseases are characterized by low serum phosphate concentration due to decreased renal phosphate reabsorption, which is associated with inappropriately normal or decreased levels of 1,25-(OH)₂D (7, 8). Therefore, tumoral calcinosis has been believed to be the clinical converse of X-linked hypophosphatemia and autosomal dominant hypophosphatemic rickets. The circulating FGF23 level, as measured by a C-terminal ELISA, is significantly increased in affected individuals with tumoral calcinosis, presumably to compensate for increased phosphate and 1,25-(OH)₂D concentrations (6). However, the increased FGF23 concentration is unable to correct these defects.

GalNAc transferase 3 belongs to a large family of Golgi-associated biosynthetic enzymes that initiates mucin-type O-glycosylation by transferring GalNAc from the sugar donor UDP-GalNAc to the hydroxyl group of a serine or threonine residue. Interestingly, a preliminary report suggests that tumoral calcinosis may be caused by the FGF23 mutation occurring at the serine residue (Ser129Phe) (9), which is a potential substrate for GalNAc transferase 3. Lastly, the present study demonstrated that, although GALNT3 has rather ubiquitous expression, GALNT3 and FGF23 are coexpressed in certain tissues such as bone and small intestine. Expression of GALNT3 in bone is particularly interesting because both FGF23 (10, 11) and PHEX (12, 13) are known to be primarily expressed in this tissue. Because polysaccharide chains attached to certain proteins are important for their proper folding and stability, these observations suggest that one potential mechanism as to how mutations in GALNT3 result in tumoral calcinosis could be that posttranslational modification of the FGF23 protein by GalNAc transferase 3 may be necessary for proper function and/or stability of FGF23. This hypothesis is consistent with severe hyperphosphatemia with high serum 1,25-(OH)₂D exhibited in Fgf23 knockout mice, in which no functional Fgf23 is present (11, 14). However, in addition to the reduced bioreactivity of FGF23, at least two other mechanisms can also explain hyperphosphatemia in patients with tumoral calcinosis: (1) resistance to FGF23 due to affected signal transduction downstream of FGF23, including the existence of decoy receptors, and (2) mechanisms unrelated to FGF23, possibly involving other phosphatonin candidates such as secreted frizzled-related protein 4 (15). Further studies are necessary to determine whether O-glycosylation of FGF23 is in fact mediated by GalNAc transferase 3.

Acknowledgments

We are indebted to current family members for their participation in this study. We thank Valeriy Parafeynikov for his technical assistance.

Footnotes

This work was supported by National Institutes of Health (NIH) Grants R01 AR42228, K24-AR02095, P01 AG18397, and R01 AR47866 (to M.J.E.), and Veterans Affairs Medical Research Service Grant AG11268, and Grant RR-30 from the Division of Research Resources, General Clinical Research Centers Program, NIH (to K.W.L.).

First Published Online February 1, 2005

Abbreviations: FGF23, Fibroblast growth factor 23; GalNAc transferase 3 or GALNT3, UDP-N-acetyl--D-galactosamine/polypeptide N-acetylgalactosaminyl transferase 3; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; 1,25-(OH)₂D, 1,25-dihydroxyvitamin D; RFLP, restriction fragment length polymorphism.

Received November 24, 2004.

Accepted January 20, 2005.

References

1. McPhaul Jr JJ, Engel FL 1961 Heterotopic calcification, hyperphosphatemia and angioid streaks of the retina. Am J Med 31:488–492[CrossRef][Medline]
2. Baldursson H, Evans EB, Dodge WF, Jackson WT 1969 Tumoral calcinosis with hyperphosphatemia. A report of a family with incidence in four siblings. J Bone Joint Surg Am 51:913–925[Abstract/Free Full Text]
3. Prince MJ, Schaeffer PC, Goldsmith RS, Chausmer AB 1982 Hyperphosphatemic tumoral calcinosis: association with elevation of serum 1,25-dihydroxycholecalciferol concentrations. Ann Intern Med 96:586–591
4. Steinherz R, Chesney RW, Eisenstein B, Metzker A, DeLuca HF, Phelps M 1985 Elevated serum calcitriol concentrations do not fall in response to hyperphosphatemia in familial tumoral calcinosis. Am J Dis Child 139:816–819[Abstract/Free Full Text]
5. Lyles KW, Burkes EJ, Ellis GJ, Lucas KJ, Dolan EA, Drezner MK 1985 Genetic transmission of tumoral calcinosis: autosomal dominant with variable clinical expressivity. J Clin Endocrinol Metab 60:1093–1096[Abstract/Free Full Text]
6. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E 2004 Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 36:579–581[CrossRef][Medline]
7. Brame LA, White KE, Econs MJ 2004 Renal phosphate wasting disorders: clinical features and pathogenesis. Semin Nephrol 24:39–47[CrossRef][Medline]
8. Econs MJ 2005 Disorders of phosphate metabolism: autosomal dominant hypophosphatemic rickets, tumor induced osteomalacia, fibrous dysplasia and the pathophysiological relevance of FGF23. In: Feldman D, Pike JW, Glorieux FH, eds. Vitamin D. 2nd ed. Burlington, MA: Elsevier Academic Press
9. Araya K, Fukumoto S, Backenroth R, Takeuchi Y, Nakayama K, Ito N, Yamazaki Y, Yamashita T, Silver J, Igarashi T, Fujita T 2004 A mutation in FGF-23 gene enhances the processing of FGF-23 protein and causes tumoral calcinosis. J Bone Miner Res 19:S41 (Abstract)
10. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P 2003 FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683–692[CrossRef][Medline]
11. Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, H JA-P, Lanske B 2004 Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 23:421–432[CrossRef][Medline]
12. Ruchon AF, Marcinkiewicz M, Siegfried G, Tenenhouse HS, DesGroseillers L, Crine P, Boileau G 1998 Pex mRNA is localized in developing mouse osteoblasts and odontoblasts. J Histochem Cytochem 46:459–468[Abstract/Free Full Text]
13. Beck L, Soumounou Y, Martel J, Krishnamurthy G, Gauthier C, Goodyer CG, Tenenhouse HS 1997 Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest 99:1200–1209[Medline]
14. Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T 2004 Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568[CrossRef][Medline]
15. Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, Jan De Beur SM, Schiavi SC, Kumar R 2003 Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest 112:785–794[CrossRef][Medline]

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This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ichikawa, S. Articles by Econs, M. J. Search for Related Content PubMed PubMed Citation Articles by Ichikawa, S. Articles by Econs, M. J. Related Collections Calcium and Bone Metabolism