Identification of two novel mutations in the GALNT3 gene in a Chinese family with hyperphosphatemic familial tumoral calcinosis.

Lihao Sun,Min Li,Lianjun Du,Lei Ye,Minjia Zhang,Peipei Zhang,Hongyan Zhao,Bei Tao,Jianmin Liu,Lin Zhao,Tingting Liu,Xiaoyi Ding

doi:10.1038/boneres.2016.38

Abstract

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal recessive genetic disease. This disease is characterized by the progressive calcification of soft tissues leading to symptoms of pressure and hyperphosphatemia but normal concentrations of serum calcium with or without an elevation of 1,25-dihydroxyvitamin D3 levels.HFTC is caused by loss-of-function mutations in the GALNT3, FGF23 or KL genes. Here, we identified two novel mutations in the GALNT3 gene in a Chinese family with HFTC. Identification of a novel genotype in HFTC provides clues for understanding the phenotype–genotype relationships in HFTC and may assist not only in the clinical diagnosis of HFTC but also in the interpretation of the genetic information used for prenatal diagnosis and genetic counseling.

Highlights

Familial tumoral calcinosis (FTC) is a rare, autosomal recessive genetic disease
FTC is caused by a lossof-function mutation in one of the following genes: FGF23, which encodes the potent phosphaturic protein fibroblast growth factor 23; GALNT3, which encodes the uridine diphosphate-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyl-transferase 3 (GalNAc-T3), a glycosyl transferase responsible for FGF23 O-glycosylation and proper secretion; or KL, which encodes Klotho, an FGF23 co-factor required to activate FGF receptors
One observed individual with Hyperphosphatemic familial tumoral calcinosis (HFTC) caused by an FGF23 mutation was Japanese

Summary

Introduction

Familial tumoral calcinosis (FTC) is a rare, autosomal recessive genetic disease. The main clinical manifestation of FTC is the development of calcified masses predominantly at peri-articular locations, especially the hips, leading to intolerable pain, skin ulcerations and secondary skin and bone infections.1According to serum phosphate concentrations, FTC can be classified as hyperphosphatemic (HFTC) or normophosphatemic FTC. FTC is caused by a lossof-function mutation in one of the following genes: FGF23, which encodes the potent phosphaturic protein fibroblast growth factor 23; GALNT3, which encodes the uridine diphosphate-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyl-transferase 3 (GalNAc-T3), a glycosyl transferase responsible for FGF23 O-glycosylation and proper secretion; or KL, which encodes Klotho, an FGF23 co-factor required to activate FGF receptors.3–7The incidences of FTC in men and women are similar; the incidence in black patients of African descent is relatively high, followed by that in white patients from the Middle East. Only one observed individual with HFTC caused by an FGF23 mutation was Japanese. we report two HFTC cases with two novel mutations in the GALNT3 gene. Familial tumoral calcinosis (FTC) is a rare, autosomal recessive genetic disease. FTC is caused by a lossof-function mutation in one of the following genes: FGF23, which encodes the potent phosphaturic protein fibroblast growth factor 23; GALNT3, which encodes the uridine diphosphate-N-acetyl-α-D-galactosamine-polypeptide N-acetylgalactosaminyl-transferase 3 (GalNAc-T3), a glycosyl transferase responsible for FGF23 O-glycosylation and proper secretion; or KL, which encodes Klotho, an FGF23 co-factor required to activate FGF receptors.. The incidences of FTC in men and women are similar; the incidence in black patients of African descent is relatively high, followed by that in white patients from the Middle East.. One observed individual with HFTC caused by an FGF23 mutation was Japanese.. We report two HFTC cases with two novel mutations in the GALNT3 gene

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